Search results for: drug targeting
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2566

Search results for: drug targeting

1966 Association of Genetically Proxied Cholesterol-Lowering Drug Targets and Head and Neck Cancer Survival: A Mendelian Randomization Analysis

Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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1965 Formulation and Optimization of Self Nanoemulsifying Drug Delivery System of Rutin for Enhancement of Oral Bioavailability Using QbD Approach

Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

Abstract:

Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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1964 Development of Extemporaneous Pediatric Syrup of Prednisone

Authors: Amel Chenafa, Sihem Boulenouar, Linda Aoued, Imane Sediri, Ismahan Djebbar, Mohamed Adil Selka

Abstract:

Introduction: The specialties intended for adults are often inadequate marketed for pediatric use, such as for a galenic form or in the dosage. For an industrial, development of a pediatric drug is confronted to various problems. So, the hospital pharmacies have to respond to adaptation needs of pharmaceutical forms for pediatric use. The objective of our work is to develop an oral form of prednisone for pediatric use since no adapted form to children is commercialized. Materials and Methods: Therefore an extemporaneous syrup of prednisone was prepared at the concentration of 0,5mg/ml from 5mg tablets and stored in amber glass bottles. Organoleptic and microbiological stability was studied in two temperatures: 5°C and 25°C, and evaluated at D0, D15, and D30. Results: No organoleptic changes have been detected on the syrup conserved at 25 and 5°C. The results show that there is no presence of bacteria, yeasts, and molds in the syrups stored at both temperatures during the analysis period. Conclusion: Sheltered from light, the developed syrup of prednisone remained stable at room temperature and/or refrigerator for 30 days.

Keywords: extemporaneous syrup, pediatric drug, prednisone, stability

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1963 Impect of Human on Prey of Birds in North West Rajasthan

Authors: Dau Lal Bohra, Sradha Vyas

Abstract:

Bird species are already showing climate-related changes in the dates they migrate and breed, and in the timing of other key life-history events. Treats of feeding managements raptors have performed important ecological, traditional and aesthetic functions throughout the Indian subcontinent. The declines in India result from elevated adult and juvenile mortality, and low breeding success. The widespread and rapid pattern of declines, i.e. in all areas irrespective of habitat or protection status suggest that persecution through shooting or poisoning, whilst important at a local scale, are unlikely to have caused the declines. A mass killing of several species of vultures in the Indian subcontinent over the last two decades is largely blamed on the presence of a drug. Veterinary diclofenac caused an unprecedented decline in South Asia’s Gyps vulture populations, with some species declining by more than 97% between 1992 and 2007. Veterinary diclofenac causes renal failure in vultures, and killed tens of millions of such birds in the Indian sub-continent. The drug was finally banned there for veterinary purposes in 2006. This drug is now ‘a global problem’ threatening many vulnerable birds of prey. Recently, stappe eagles are also susceptible to veterinary diclofenac, effectively increasing the potential threat level, and the risks for European biodiversity. Steppe eagles are closely related with golden eagles (Aquila chrysaetus), imperial eagles (Aquila heliaca) and Spanish imperial eagles (Aquila adalberti), and all these species scavenge opportunistically on carcasses throughout their range. The Spanish imperial eagle, considered Vulnerable at global level, is now particularly at risk, due to the availability of diclofenac in Spain. These findings strengthen the case for banning veterinary diclofenac across. From year 2011 to 2014 more than 300 hundred birds dead in jorbeer, Bikaner. Now, with unequivocal evidence that this veterinary drug can cause a much wider impact on Europe´s biodiversity, it is time for action – please ban diclofenac human brand also in multi-dose vial from market.

Keywords: mortility, prey of birds, diclofenac, Rajasthan

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1962 Formulation and In vivo Evaluation of Venlafaxine Hydrochloride Long Acting Tablet

Authors: Abdulwahhab Khedr, Tamer Shehata, Hanaa El-Ghamry

Abstract:

Venlafaxine HCl is a novel antidepressant drug used in the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder. Conventional therapeutic regimens with venlafaxine HCl immediate-release dosage forms require frequent dosing due to short elimination half-life of the drug and reduced bioavailability. Hence, this study was carried out to develop sustained-release dosage forms of venlafaxine HCl to reduce its dosing frequency, to improve patient compliance and to reduce side effects of the drug. The polymers used were hydroxypropylmethyl cellulose, xanthan gum, sodium alginate, sodium carboxymethyl cellulose, Carbopol 940 and ethyl cellulose. The physical properties of the prepared tablets including tablet thickness, diameter, weight uniformity, content uniformity, hardness and friability were evaluated. Also, the in-vitro release of venlafaxine HCl from different matrix tablets was studied. Based on physical characters and in-vitro release profiles, certain formulae showing promising sustained-release profiles were subjected to film coating with 15% w/v EC in dichloromethane/ethanol mixture (1:1 ratio) using 1% w/v HPMC as pore former and 30% w/w dibutyl phthalate as plasticizer. The optimized formulations were investigated for drug-excipient compatibility using FTIR and DSC studies. Physical evaluation of the prepared tablets fulfilled the pharmacopoeial requirements for tablet friability test, where the weight loss of the prepared formulae did not exceed 1% of the weight of the tested tablets. Moderate release was obtained from tablets containing HPMC. FTIR and DSC studies for such formulae revealed the absence of any type of chemical interaction between venlafaxine HCl and the used polymers or excipients. Forced swimming test in rats was used to evaluate the antidepressant activity of the selected matrix tablets of venlafaxine HCl. Results showed that formulations significantly decreased the duration of animals’ immobility during the 24 hr-period of the test compared to non-treated group.

Keywords: antidepressant, sustained-release, matrix tablet, venlafaxine hydrochloride

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1961 Multiple Approaches for Ultrasonic Cavitation Monitoring of Oxygen-Loaded Nanodroplets

Authors: Simone Galati, Adriano Troia

Abstract:

Ultrasound (US) is widely used in medical field for a variety diagnostic techniques but, in recent years, it has also been creating great interest for therapeutic aims. Regarding drug delivery, the use of US as an activation source provides better spatial delivery confinement and limits the undesired side effects. However, at present there is no complete characterization at a fundamental level of the different signals produced by sono-activated nanocarriers. Therefore, the aim of this study is to obtain a metrological characterization of the cavitation phenomena induced by US through three parallel investigation approaches. US was focused into a channel of a customized phantom in which a solution with oxygen-loaded nanodroplets (OLNDs) was led to flow and the cavitation activity was monitored. Both quantitative and qualitative real-time analysis were performed giving information about the dynamics of bubble formation, oscillation and final implosion with respect to the working acoustic pressure and the type of nanodroplets, compared with pure water. From this analysis a possible interpretation of the observed results is proposed.

Keywords: cavitation, drug delivery, nanodroplets, ultra-sound

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1960 Quince Seed Mucilage (QSD)/ Multiwall Carbonano Tube Hybrid Hydrogels as Novel Controlled Drug Delivery Systems

Authors: Raouf Alizadeh, Kadijeh Hemmati

Abstract:

The aim of this study is to synthesize several series of hydrogels from combination of a natural based polymer (Quince seed mucilage QSD), a synthetic copolymer contained methoxy poly ethylene glycol -polycaprolactone (mPEG-PCL) in the presence of different amount of multi-walled carbon nanotube (f-MWNT). Mono epoxide functionalized mPEG (mP EG-EP) was synthesized and reacted with sodium azide in the presence of NH4Cl to afford mPEG- N3(-OH). Then ring opening polymerization (ROP) of ε–caprolactone (CL) in the presence of mPEG- N3(-OH) as initiator and Sn(Oct)2 as catalyst led to preparation of mPEG-PCL- N3(-OH ) which was grafted onto propagylated f-MWNT by the click reaction to obtain mPEG-PCL- f-MWNT (-OH ). In the presence of mPEG- N3(-Br) and mixture of NHS/DCC/ QSD, hybrid hydrogels were successfully synthesized. The copolymers and hydrogels were characterized using different techniques such as, scanning electron microscope (SEM) and thermogravimetric analysis (TGA). The gel content of hydrogels showed dependence on the weight ratio of QSD:mPEG-PCL:f-MWNT. The swelling behavior of the prepared hydrogels was also studied under variation of pH, immersion time, and temperature. According to the results, the swelling behavior of the prepared hydrogels showed significant dependence in the gel content, pH, immersion time and temperature. The highest swelling was observed at room temperature, in 60 min and at pH 8. The loading and in-vitro release of quercetin as a model drug were investigated at pH of 2.2 and 7.4, and the results showed that release rate at pH 7.4 was faster than that at pH 2.2. The total loading and release showed dependence on the network structure of hydrogels and were in the range of 65- 91%. In addition, the cytotoxicity and release kinetics of the prepared hydrogels were also investigated.

Keywords: antioxidant, drug delivery, Quince Seed Mucilage(QSD), swelling behavior

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1959 Biosynthesis, Characterization and Interplay of Bacteriocin-nanoparticles to Combat Infectious Drug Resistant Pathogens

Authors: Asma Ansari, Afsheen Aman, Shah Ali Ul Qader

Abstract:

In the past few years, numerous concerns have been raised against increased bacterial resistance towards effective drugs and become a debated issue all over the world. With the emergence of drug resistant pathogens, the interaction of natural antimicrobial compounds and antibacterial nanoparticles has emerged as a potential candidate for combating infectious diseases. Microbial diversity in the biome provides an opportunity to screen new species which are capable of producing large number of antimicrobial compounds. Among these antimicrobial compounds, bacteriocins are highly specific and efficient antagonists. A combination of bacteriocin along with nanoparticles could prove to be more potent due to broadened antibacterial spectrum with possibly lower doses. In the current study, silver nanoparticles were synthesized through biological reduction using various isolated bacterial, fungal and yeast strains. Spectroscopy and scanning electron microscopy (SEM) was performed for the confirmation of nanoparticles. Bacteriocin was characterized and purified to homogeneity through gel permeation chromatography. The estimated molecular weight of bacteriocin was 10 kDa. Amino acid analysis and N-terminal sequencing revealed the novelty of the protein. Then antibacterial potential of silver nanoparticles and broad inhibitory spectrum bacteriocin was determined through agar well diffusion assay. These synthesized bacteriocin-Nanoparticles exhibit a good potential for clinical applications as compared to bacteriocin alone. This combination of bacteriocin with nanoparticles will be used as a new sort of biocide in the field of nano-proteomics. The advancement of nanoparticles-mediated drug delivery system will open a new age for rapid eradication of pathogens from biological systems.

Keywords: BAC-IB17, multidrug resistance, purification, silver nanoparticles

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1958 Electrospinning of Nanofibrous Meshes and Surface-Modification for Biomedical Application

Authors: Hyuk Sang Yoo, Young Ju Son, Wei Mao, Myung Gu Kang, Sol Lee

Abstract:

Biomedical applications of electrospun nanofibrous meshes have been received tremendous attentions because of their unique structures and versatilities as biomaterials. Incorporation of growth factors in fibrous meshes can be performed by surface-modification and encapsulation. Those growth factors stimulate differentiation and proliferation of specific types of cells and thus lead tissue regenerations of specific cell types. Topographical cues of electrospun nanofibrous meshes also increase differentiation of specific cell types according to alignments of fibrous structures. Wound healing treatments of diabetic ulcers were performed using nanofibrous meshes encapsulating multiple growth factors. Aligned nanofibrous meshes and those with random configuration were compared for differentiating mesenchymal stem cells into neuronal cells. Thus, nanofibrous meshes can be applied to drug delivery carriers and matrix for promoting cellular proliferation.

Keywords: nanofiber, tissue, mesh, drug

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1957 Healthcare Professionals' Perspectives on Warfarin Therapy at Lao-Luxembourg Heart Centre, Mahosot Hospital, Lao PDR

Authors: Vanlounni Sibounheuang, Wanarat Anusornsangiam, Pattarin Kittiboonyakun, Chanthanom Manithip

Abstract:

In worldwide, one of the most common use of oral anticoagulant is warfarin. Its margin between therapeutic inhibition of clot formation and bleeding complications is narrow. Mahosot Hospital, warfarin clinic had not been established yet. The descriptive study was conducted by investigating drug-related problems of outpatients using warfarin, the value of the international normalized ratio (INR) higher than normal ranges (25.40 % of the total 272 outpatients) were mostly identified at Lao-Luxembourg Heart Centre, Mahosot Hospital, Lao PDR. This result led to the present study conducting qualitative interviews in order to help establish a warfarin clinic at Mahosot Hospital for the better outcomes of patients using warfarin. The purpose of this study was to explore perspectives of healthcare professional providing services for outpatients using warfarin. The face to face, in-depth interviews were undertaken among nine healthcare professionals (doctor=3, nurse=3, pharmacist=3) working at out-patient clinic, Lao-Luxembourg Heart Centre, Mahosot Hospital, Lao PDR. The interview guides were developed, and they were validated by the experts in the fields of qualitative research. Each interview lasted approximately 20 minutes. Three major themes emerged; healthcare professional’s experiences of current practice problems with warfarin therapy, healthcare professionals’ views of medical problems related to patients using warfarin, and healthcare professionals’ perspectives on ways of service improvement. All healthcare professionals had the same views that it’s difficult to achieve INR goal for individual patients because of some important patient barriers especially lack of knowledge about to use warfarin properly and safety, patients not regularly follow-up due to problems with transportations and financial support. Doctors and nurses agreed to have a pharmacist running a routine warfarin clinic and provided counselling to individual patients on the following points: how to take drug properly and safety, drug-drug and food-drug interactions, common side effects and how to manage them, lifestyle modifications. From the interviews, some important components of the establishment of a warfarin clinic included financial support, increased human resources, improved the system of keeping patients’ medical records, short course training for pharmacists. This study indicated the acceptance of healthcare professionals on the important roles of pharmacists and the feasibility of setting up warfarin clinic by working together with the multidisciplinary health care team in order to help improve health outcomes of patients using warfarin at Mahosot Hospital, Lao PDR.

Keywords: perspectives, healthcare professional, warfarin therapy, Mahosot Hospital

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1956 Optimizing the Effectiveness of Docetaxel with Solid Lipid Nanoparticles: Formulation, Characterization, in Vitro and in Vivo Assessment

Authors: Navid Mosallaei, Mahmoud Reza Jaafari, Mohammad Yahya Hanafi-Bojd, Shiva Golmohammadzadeh, Bizhan Malaekeh-Nikouei

Abstract:

Background: Docetaxel (DTX), a potent anticancer drug derived from the European yew tree, is effective against various human cancers by inhibiting microtubule depolymerization. Solid lipid nanoparticles (SLNs) have gained attention as drug carriers for enhancing drug effectiveness and safety. SLNs, submicron-sized lipid-based particles, can passively target tumors through the "enhanced permeability and retention" (EPR) effect, providing stability, drug protection, and controlled release while being biocompatible. Methods: The SLN formulation included biodegradable lipids (Compritol and Precirol), hydrogenated soy phosphatidylcholine (H-SPC) as a lipophilic co-surfactant, and Poloxamer 188 as a non-ionic polymeric stabilizer. Two SLN preparation techniques, probe sonication and microemulsion, were assessed. Characterization encompassed SLNs' morphology, particle size, zeta potential, matrix, and encapsulation efficacy. In-vitro cytotoxicity and cellular uptake studies were conducted using mouse colorectal (C-26) and human malignant melanoma (A-375) cell lines, comparing SLN-DTX with Taxotere®. In-vivo studies evaluated tumor inhibitory efficacy and survival in mice with colorectal (C-26) tumors, comparing SLNDTX withTaxotere®. Results: SLN-DTX demonstrated stability, with an average size of 180 nm and a low polydispersity index (PDI) of 0.2 and encapsulation efficacy of 98.0 ± 0.1%. Differential scanning calorimetry (DSC) suggested amorphous encapsulation of DTX within SLNs. In vitro studies revealed that SLN-DTX exhibited nearly equivalent cytotoxicity to Taxotere®, depending on concentration and exposure time. Cellular uptake studies demonstrated superior intracellular DTX accumulation with SLN-DTX. In a C-26 mouse model, SLN-DTX at 10 mg/kg outperformed Taxotere® at 10 and 20 mg/kg, with no significant differences in body weight changes and a remarkably high survival rate of 60%. Conclusion: This study concludes that SLN-DTX, prepared using the probe sonication, offers stability and enhanced therapeutic effects. It displayed almost same in vitro cytotoxicity to Taxotere® but showed superior cellular uptake. In a mouse model, SLN-DTX effectively inhibited tumor growth, with 10 mg/kg outperforming even 20 mg/kg of Taxotere®, without adverse body weight changes and with higher survival rates. This suggests that SLN-DTX has the potential to reduce adverse effects while maintaining or enhancing docetaxel's therapeutic profile, making it a promising drug delivery strategy suitable for industrialization.

Keywords: docetaxel, Taxotere®, solid lipid nanoparticles, enhanced permeability and retention effect, drug delivery, cancer chemotherapy, cytotoxicity, cellular uptake, tumor inhibition

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1955 Pharmacogenetics Study of Dapsone-Induced Severe Cutaneous Adverse Reactions and HLA Class I Alleles in Thai Patients

Authors: Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Jettanong Klaewsongkram, Chonlaphat Sukasem

Abstract:

Dapsone (4, 4’-diaminodiphenyl sulfone, DDS) is broadly used for the treatment of inflammatory diseases and infections such as; leprosy, Pneumocystis jiroveci pneumonia in patients with HIV infection, neutrophilic dermatoses, dermatitis herpetiformis and autoimmune bullous disease. The severe cutaneous adverse drug reactions (SCARs) including, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are rare but severe life-threatening adverse drug reactions. Dapsone is one of many culprit drugs induced SJS, TEN and DRESS. Notwithstanding, to our knowledge, there are no studies of the association of HLA class I alleles and dapsone-induced SCARs in non-leprosy Thai patients. This investigation was a prospective cohort study, which performed in a total of 45 non-leprosy patients. Fifteen patients of dapsone-induced SCARs were classified as following the RegiSCAR criteria, and 30 dapsone-tolerant controls were exposed to dapsone more than 6 months without any evidence of cutaneous reactions. The genotyping of HLA-A, -B and –C were performed using sequence-specific oligonucleotides (PCR-SSOs). The Ethics Committee of Ramathibodi hospital, Mahidol University, approved this study. Among all HLA class I alleles, HLA-A*24:07, HLA-B*13:01, HLA-B*15:02, HLA-C*03:04 and HLA-C*03:09 were significantly associated with dapsone-induced SCARs (OR = 10.55, 95% CI = 1.06 – 105.04, p = 0.0360; OR = 56.00, 95% CI = 8.27 – 379.22, p = 0.0001; OR = 7.00, 95% CI = 1.17 – 42.00, p = 0.0322; OR = 6.00, 95% CI = 1.24 – 29.07, p = 0.0425 and OR = 17.08, 95% CI = 0.82 – 355.45, p = 0.0321, respectively). Furthermore, HLA-B*13:01 allele had strong association with dapsone-induced SJS-TEN and DRESS when compared with dapsone-tolerant controls (OR = 42.00, 95% CI = 2.88 – 612.31, p = 0.0064 and OR = 63.00, 95% CI = 7.72 – 513.94 and p = 0.0001, respectively). Consequently, HLA-B*13:01 might serve as a pharmacogenetic marker for screening before initiating the therapy with dapsone for prevention of dapsone-induced SCARs.

Keywords: dapsone-induced SCARs, HLA-B*13:01, HLA class I alleles, severe cutaneous adverse reactions, Thai

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1954 Formulation and Optimization of Topical 5-Fluorouracil Microemulsions Using Central Compisite Design

Authors: Sudhir Kumar, V. R. Sinha

Abstract:

Water in oil topical microemulsions of 5-FU were developed and optimized using face centered central composite design. Topical w/o microemulsion of 5-FU were prepared using sorbitan monooleate (Span 80), polysorbate 80 (Tween 80), with different oils such as oleic acid (OA), triacetin (TA), and isopropyl myristate (IPM). The ternary phase diagrams designated the microemulsion region and face centered central composite design helped in determining the effects of selected variables viz. type of oil, smix ratio and water concentration on responses like drug content, globule size and viscosity of microemulsions. The CCD design exhibited that the factors have statistically significant effects (p<0.01) on the selected responses. The actual responses showed excellent agreement with the predicted values as suggested by the CCD with lower residual standard error. Similarly, the optimized values were found within the range as predicted by the model. Furthermore, other characteristics of microemulsions like pH, conductivity were investigated. For the optimized microemulsion batch, ex-vivo skin flux, skin irritation and retention studies were performed and compared with marketed 5-FU formulation. In ex vivo skin permeation studies, higher skin retention of drug and minimal flux was achieved for optimized microemulsion batch then the marketed cream. Results confirmed the actual responses to be in agreement with predicted ones with least residual standard errors. Controlled release of drug was achieved for the optimized batch with higher skin retention of 5-FU, which can further be utilized for the treatment of many dermatological disorders.

Keywords: 5-FU, central composite design, microemulsion, ternanry phase diagram

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1953 Protective Effect of Levetiracetam on Aggravation of Memory Impairment in Temporal Lobe Epilepsy by Phenytoin

Authors: Asher John Mohan, Krishna K. L.

Abstract:

Objectives: (1) To assess the extent of memory impairment induced by Phenytoin (PHT) at normal and reduced dose on temporal lobe epileptic mice. (2) To evaluate the protective effect of Levetiracetam (LEV) on aggravation of memory impairment in temporal lobe epileptic mice by PHT. Materials and Methods: Albino mice of either sex (n=36) were used for the study for a period of 64 days. Convulsions were induced by intraperitoneal administration of pilocarpine 280 mg/kg on every 6th day. Radial arm maze (RAM) was employed to evaluate the memory impairment activity on every 7th day. The anticonvulsant and memory impairment activity were assessed in PHT normal and reduced doses both alone and in combination with LEV. RAM error scores and convulsive scores were the parameters considered for this study. Brain acetylcholine esterase and glutamate were determined along with histopathological studies of frontal cortex. Results: Administration of PHT for 64 days on mice has shown aggravation of memory impairment activity on temporal lobe epileptic mice. Although the reduction in PHT dose was found to decrease the degree of memory impairment the same decreased the anticonvulsant potency. The combination with LEV not only brought about the correction of impaired memory but also replaced the loss of potency due to the reduction of the dose of the antiepileptic drug employed. These findings were confirmed with enzyme and neurotransmitter levels in addition to histopathological studies. Conclusion: This study thus builds a foundation in combining a nootropic anticonvulsant with an antiepileptic drug to curb the adverse effect of memory impairment associated with temporal lobe epilepsy. However further extensive research is a must for the practical incorporation of this approach into disease therapy.

Keywords: anti-epileptic drug, Phenytoin, memory impairment, Pilocarpine

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1952 Proniosomes as a Carrier for Ocular Drug Delivery

Authors: Rawia M. Khalil, Ghada Abd-Elbary, Mona Basha, Ghada E. A. Awad, Hadeer A. Elhashemy

Abstract:

Background: Bacterial infections of the eye are the clinical conditions responsible for ocular morbidity and blindness. Conjunctivitis is an inflammation of the conjunctiva, due to Staphylococcus aureus. Lomefloxacin HCl (LXN) is a third generation flouroquinolone antibiotic with a broad spectrum against wide range of bacteria and very effective against Staph infections especially in conjunctiva (conjunctivitis). The present study aims to develop and evaluate novel ocular proniosomal gels of Lomefloxacin Hcl (LXN); in order to improve its ocular bioavailability for the management of bacterial conjunctivitis. Materials and methods: Proniosomes were prepared by coacervation phase separation method using different types of nonionic surfactants (Span 60,40,20,Tween 20,40,60,80,Brij 35,98,72) solely and as mixtures with Span® 60. The formed gels were characterized for entrapment efficiency, vesicle size and in vitro drug release. The optimum proniosomal gel; P-LXN 7 were characterized for pH measurement, transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) as well as Stability study and microbiological evaluation .The results revealed that only Span 60 was able to form stable LXN proniosomal gel when used individually while the other nonionic surfactants formed gels only in combination with Span 60 at different ratios. The optimum proniosomal gel; P-LXN 7 (Span60:Tween60, 9:1) appeared as spherical shaped vesicles having high entrapment efficiency (>80 %), appropriate vesicle size (187 nm) as well as controlled drug release over 12h. DSC confirmed the amorphous nature and the uniformity of LXN inclusion within the vesicles. Physical stability study did not show any significant changes in appearance or entrapment efficiency or vesicle size after storage for 3 months at 4°C. Ocular irritancy test revealed that P-LXN 7 was safe, well tolerable and suitable for ocular delivery. In vivo antibacterial activity of P-LXN 7 evaluated using the susceptibility test and topical therapy of induced ocular conjunctivitis confirmed the enhanced antibacterial therapeutic efficacy of the LXN-proniosomal gel compared to the commercially available LXN eye drops; Orchacin®. Conclusions: Our results suggest that proniosomal gels could provide a promising carrier of LXN for efficient ocular treatment of bacterial conjunctivitis.

Keywords: bacterial conjunctivitis, lomefloxacin HCl, ocular drug delivery, proniosomes

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1951 Determinants of Multidrug-Resistant Tuberculosis in Patients Who Underwent First-Line Treatment in Addis Ababa: A Case Control Study

Authors: Selamawit Hirpa, Girmay Medhin, Belaineh Girma, Muluken Melese, Alemayehu Mekonen, Pedro Suarez, Gobena Ameni

Abstract:

Worldwide, there were 650,000 multi-drug resistant tuberculosis (MDR-TB) cases in 2010. Ethiopia is 15th among the 27 MDR-TB high-burden countries. A case control study was conducted at St. Peter Hospital and five health centers in Addis Ababa. Cases were MDR-TB patients who were in treatment at St. Peter Hospital during the study period. Controls were patients who were on first-line anti-TB treatment and were registered as cured or having completed treatment in the period 9 April 2009– 28 February 2010, in five health centers. A structured interview questionnaire was used to assess factors that could potentially be associated with the occurrence of MDR-TB. Factors that were significantly associated with MDR-TB: drug side effects during first-line treatment (adjusted odds ratio (AOR): 4.5, 95% CI; 1.9 - 10.5); treatment not directly observed by a health worker (AOR = 11.7, 95% CI; 4–34.3); and retreatment with the Category II regimen (P = 0.000).

Keywords: adherence to TB treatment, MDR-TB, TB treatment, TB treatment regimens

Procedia PDF Downloads 501
1950 Substance Use and Association of Adverse Childhood Experience and Mental Health in Young Adults

Authors: Sreelekha Prakash, Yulong Gu

Abstract:

Background: About 61% of adults surveyed across 25 states reported they had experienced at least one type of Adverse Childhood Experience (ACE) before 18 years of age. Relationships between ACEs and a variety of substance-related behaviors and behavioral health have been reported in previous studies. ACEs can have lasting, negative effects on health, well-being, as well as life opportunities such as education and job potential. Objectives: For the current research, the aim was to assess the factors affecting substance use behavior in young adults. The further onset of drug use and its association was analyzed with ACEs and mental health. Method: The young adults from a county in the north-eastern United States were invited to participate in an online questionnaire survey with prior consent through an IRB approved study. The Survey included questions related to social determinants of health, 10 item ACE questionnaire, and substance use related to Alcohol, Marijuana, Opioids, Stimulants, and other drugs. PHQ-9 questionnaire was used to assess cognitive health. Results: Data was analyzed for the 244 completed surveys {68% (165) were females, and 78% (190) were Whites}. The average age of the participants was 26.7 years, and approximately 80% were lifelong residents of the county or year-round residents. Of the respondents, 50% (122) were high school graduates with some college education, and 56% (136) had a full-time jobs. Past 30-day usage for alcohol was 76% (72), and marijuana was 28.4% (27). The data showed that the higher the ACE scores, the younger they start using any substance (p < 0.0001). The data for PHQ-9 and ACE scores showed that the higher the ACE score, the higher the PHQ-9 score, with a significant p-value (p 0.0001). The current data also showed a significant association with other drugs; marijuana use showed significance for 30 days of use (p 0.0001), stimulant use (0.0008), prescription drug misuse (0.01), and opioids (0.01). Conclusion: These findings further support the association between ACEs and initiation of drug use and its correlation with mental health symptoms. Promoting a safe and supportive environment for children and youth in their earlier ages can prevent the youth and young adults from the effects of drug use and create healthy living habits for young adults.

Keywords: subtance use, young adults, adverse childhood experience, PHQ-9

Procedia PDF Downloads 86
1949 The Effect of a Three-Month Training Program on the Back Kyphosis of Former Male Addicts

Authors: M. J. Pourvaghar, Sh. Khoshemehry

Abstract:

Adopting inappropriate body posture during addiction can cause muscular and skeletal deformities. This study is aimed at investigating the effects of a program of the selected corrective exercises on the kyphosis of addicted male patients. Materials and methods: This was a quasi-experimental study. This study has been carried out using the semi-experimental method. The subjects of the present study included 104 addicted men between 25 to 45 years of age. In 2014, these men were referred to one of the NA (Narcotic Anonymous) centres in Kashan in 2015. A total of 24 people suffering from drug withdrawal, who had abnormal kyphosis, were purposefully selected as a sample. The sample was randomly divided into two groups, experimental and control; each group consisted of 12 people. The experimental group participated in a training program for 12 weeks consisting of three 60 minute sessions per week. That includes strengthening, stretching and PNF exercises (deep stretching of the muscle). The control group did no exercise or corrective activity. The Kolmogorov-Smirnov test was used to assess normal distribution of data; and a paired t-test and covariance analysis test were used to assess the effectiveness of the exercises, with a significance level of P≤0.05 by using SPSS18. The results showed that three months of the selected corrective exercises had a significant effect (P≤ 0.005) on the correction of the kyphosis of the addicted male patients after three months of rehabilitation (drug withdrawal) in the experimental group, while there was no significant difference recorded in the control group (P≥0.05). The results show that exercise and corrective activities can be used as non-invasive and non-pharmacological methods to rehabilitate kyphosis abnormalities after drug withdrawal and treatment for addiction.

Keywords: kyphosis, exercise-rehabilitation, addict, addiction

Procedia PDF Downloads 280
1948 Factors Associated with Non-Adherence to Antiretroviral Treatment among HIV Infected Patients in Ukraine

Authors: Larissa Burruano, Sergey Grabovyj, Irina Nguen

Abstract:

The study aimed to assess the level of adherence to anti retroviral therapy (ART) and to examine the relationship between adherence and risk behavior factor (drug use) among patients infected with HIV. The patients with newly diagnosed or established HIV infection under follow-up at the Sumskij Regional Centre for AIDS Prevention in Ukraine were eligible for this study. Medical records were used to measure the patient’s adherence to medication. Measurements were obtained at month 6 and at month 12 to calculate the number of medication omission during the past 30 days: (on a 2-point scale – once until three in a month – were considered adherent, three and more in a month – were considered non-adherent). Of the 50 study participants, 27 (54.0%) were men and 23 (46.0%) women. The mean age is 35.2 years (SD= 5.1). A majority of the patients (82.0%) is in the age group of 25-30 years. The main level of adherence was 74.0% and 66.0% at 6 and 12 months, respectively. The main routes of HIV transmission were drug injection among men 12 (44.4%) and sexual contact among women 11 (47.8%). Univariate analyses indicated that patients who had lower level of education were more likely to have been non-adherent at month 6- (X2 =5.1, n=50, p < .05) and at month 12 (X2 = 4.34, n=50, p < .05). Multivariate tests showed that only age (OR= 1.163 [95% CI 0.98–1.370]) was significant independent predictor of treatment adherence, while gender, education, employment status were not predictive for the risk of developing non-compliance. There was not a significant interaction between non-adherence and intravenous drug use. Consistent with these findings, younger people were more likely to have missed a dose of their medication because they had a greater sense of invulnerability than older patients. The study indicates that the socio demographic characteristic should be taken into an account in the future research regarding adherence in the case of HIV infection. If the patient anti retroviral adherence can be improved by qualitatively better medical care in all regions of the Ukraine, behavioral changes in the population can to be expected in the long term.

Keywords: HIV, antiretroviral therapy, adherence, Ukraine, Eastern Europe

Procedia PDF Downloads 289
1947 Concept Mapping to Reach Consensus on an Antibiotic Smart Use Strategy Model to Promote and Support Appropriate Antibiotic Prescribing in a Hospital, Thailand

Authors: Phenphak Horadee, Rodchares Hanrinth, Saithip Suttiruksa

Abstract:

Inappropriate use of antibiotics has happened in several hospitals, Thailand. Drug use evaluation (DUE) is one strategy to overcome this difficulty. However, most community hospitals still encounter incomplete evaluation resulting overuse of antibiotics with high cost. Consequently, drug-resistant bacteria have been rising due to inappropriate antibiotic use. The aim of this study was to involve stakeholders in conceptualizing, developing, and prioritizing a feasible intervention strategy to promote and support appropriate antibiotic prescribing in a community hospital, Thailand. Study antibiotics included four antibiotics such as Meropenem, Piperacillin/tazobactam, Amoxicillin/clavulanic acid, and Vancomycin. The study was conducted for the 1-year period between March 1, 2018, and March 31, 2019, in a community hospital in the northeastern part of Thailand. Concept mapping was used in a purposive sample, including doctors (one was an administrator), pharmacists, and nurses who involving drug use evaluation of antibiotics. In-depth interviews for each participant and survey research were conducted to seek the problems for inappropriate use of antibiotics based on drug use evaluation system. Seventy-seven percent of DUE reported appropriate antibiotic prescribing, which still did not reach the goal of 80 percent appropriateness. Meropenem led other antibiotics for inappropriate prescribing. The causes of the unsuccessful DUE program were classified into three themes such as personnel, lack of public relation and communication, and unsupported policy and impractical regulations. During the first meeting, stakeholders (n = 21) expressed the generation of interventions. During the second meeting, participants who were almost the same group of people in the first meeting (n = 21) were requested to independently rate the feasibility and importance of each idea and to categorize them into relevant clusters to facilitate multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the idealist, cluster list, point map, point rating map, cluster map, and cluster rating map. All of these were distributed to participants (n = 21) during the third meeting to reach consensus on an intervention model. The final proposed intervention strategy included 29 feasible and crucial interventions in seven clusters: development of information technology system, establishing policy and taking it into the action plan, proactive public relations of the policy, action plan and workflow, in cooperation of multidisciplinary teams in drug use evaluation, work review and evaluation with performance reporting, promoting and developing professional and clinical skill for staff with training programs, and developing practical drug use evaluation guideline for antibiotics. These interventions are relevant and fit to several intervention strategies for antibiotic stewardship program in many international organizations such as participation of the multidisciplinary team, developing information technology to support antibiotic smart use, and communication. These interventions were prioritized for implementation over a 1-year period. Once the possibility of each activity or plan is set up, the proposed program could be applied and integrated into hospital policy after evaluating plans. Effectiveness of each intervention could be promoted to other community hospitals to promote and support antibiotic smart use.

Keywords: antibiotic, concept mapping, drug use evaluation, multidisciplinary teams

Procedia PDF Downloads 118
1946 Attitudes toward Sexual Assault: The Role of Religious Affiliation, Alcohol, and Gender

Authors: Ignacio Luis Ramirez, Brittney Holcomb

Abstract:

This study examines attitudes toward sexual assault based on religious affiliation, religiosity, religious beliefs, attitude about sexual assault education, alcohol, and drug use. This study found respondents who identified themselves as Catholics had more negative attitudes toward sexual assault and were more likely to support victim-blaming statements than Baptists or Protestants. Respondents who indicated a greater problem with alcohol had more negative attitudes toward sexual assault and were more likely to support victim-blaming statements. In reference to gender, males had more negative attitudes toward sexual assault and were more likely to support victim-blaming statements than females. The respondent’s religiosity and religious beliefs did not affect their attitudes toward sexual assault. Additionally, attitudes about sexual assault education and drug use did not affect attitudes toward sexual assault.

Keywords: sexual assault, religion, education, alcohol, drugs

Procedia PDF Downloads 179
1945 Officinal Quality Assurance: Investigation near the Pharmacists Dispensary at Oran- Algeria

Authors: S. Boulenouar, A. Boukli Hacene, S. Brahmi

Abstract:

Quality is an old concept but which recently became omnipresent in the society. It is a pledge of the well done job and therefore the satisfaction of the customer. Now, dispensing pharmacies seem to be held away from this approach. Officinal staff is called to dispense drugs. However this essential function is rarely studied and taken into account. To contribute to the good use of medicines and to reduce the dangers, it is important to consider the dispensation of drugs practised in the pharmacies. It is a both descriptive and retrospective study .The descriptive part is to conduct a survey near to the dispensary pharmacists. The retrospective section concentrates on the analysis of medicine prescriptions dispensed to patients. Following the survey that we carried out near the pharmacists of dispensary of the town of Oran, it appears that in majority, they are not inclined, by themselves, to take up the challenge of quality at the dispensary. The approach requires time and a motivation that pharmacists do not have for the moment. Efforts are still needed on the part of pharmacists, but also of authorities and organizations in charge of quality in the dispensary. At the end of this work, it seems to us that the implementation of a quality approach is part of our reflection on the added value of the pharmacist of dispensary in the drug chain.

Keywords: customer satisfaction, dispensary, dispensing of the drug, quality approach

Procedia PDF Downloads 319
1944 Polymer Composites Of MOF-5 For Efficient and Sustained Delivery of Cephalexin and Metronidazole

Authors: Anoff Anim, Lila Mahmoud, Maria Katsikogianni, Sanjit Nayak

Abstract:

Sustained and controlled delivery of antimicrobial drugs have been largely studied recently using metal organic frameworks (MOFs)and different polymers. However, much attention has not been given to combining both MOFs and biodegradable polymers, which would be a good strategy in providing a sustained gradual release of the drugs. Herein, we report a comparative study of the sustained and controlled release of widely used antibacterial drugs, cephalexin and metronidazole, from zinc-based MOF-5 incorporated in biodegradable polycaprolactone (PCL) and poly-lactic glycolic acid (PLGA) membranes. Cephalexin and metronidazole were separately incorporated in MOF-5 post-synthetically, followed by their integration into biodegradable PLGA and PCL membranes. The pristine MOF-5 and the loaded MOFs were thoroughly characterized by FT-IR, SEM, TGA and PXRD. Drug release studies were carried out to assess the release rate of the drugs in PBS and distilled water for up to 48 hours using UV-Vis Spectroscopy. Four bacterial strains from both the Gram-positive and Gram-negative types, Staphylococus aureus, Staphylococuss epidermidis, Escherichia coli, Acinetobacter baumanii, were tested against the pristine MOF, pure drugs, loaded MOFs and the drug-loaded MOF-polymer composites. Metronidazole-loaded MOF-5 composite of PLGA (PLGA-Met@MOF-5) was found to show highest efficiency to inhibit the growth of S. epidermidis compared to the other bacteria strains while maintaining a sustained minimum inhibitory concentration (MIC). This study demonstrates that the combination of biodegradable MOF-polymer composites can provide an efficient platform for sustained and controlled release of antimicrobial drugs and can be a potential strategy to integrate them in biomedical devices.

Keywords: antimicrobial resistance, biodegradable polymers, cephalexin, drug release metronidazole, MOF-5, PCL, PLGA

Procedia PDF Downloads 133
1943 Taking Risks to Get Pleasure: Reproductive Health Behaviour of Early Adolescents in Pantura Line, Indonesia

Authors: Juariah Salam Suryadi

Abstract:

North coast (Pantura) line is known as a high-risk area related to reproductive health. This is because along the line, there are many food stalls and entertainment industries that at night the function changed to be sexual transaction areas. This business line also facilitate circulation and transaction of drug and substance abuse. The environment conditions can influence adolescents who live in this area. It is because of adolescence characteristics that has high curiosity and looking for their identities. Therefore, purposes of this study were to explore reproductive health behaviour of early adolescents who lived in Pantura line and to suggest intervention based on the adolescents reproductive health conditions. This study was conducted in November 2016 among the seventh-grade students of Pusakajaya Junior High School 1 and 2, Subang District. Number of respondents were 269 students (Male=135, Female=134). The students were interviewed using a semi-structured questionnaire. Some teachers also interviewed to complement the data. The quantitative data was analyzed with univariate analysis, while content analysis was used for the qualitative data. Findings of this study showed that 85,2% of male students were smoker. Most of them started smoking at elementary school. Male students who often drunk alcohol were about 25,2% and all of them initiated to drink at elementary school. There were about 21,5% of male students ever used drug and substance abuse. There were 54,6% of the students that confessed having a lover. Most of them were female students. Sexual behaviour that ever done with their lovers were: holding hands (37,4%), kissing (4%) and embracing (6,8%). Although all of the students claimed to have never had sexual intercourse, but 5,9% of them said that they had friends who have had sexual intercourse. Most of the students also had friends with negative characteristics. Their friends were smoker (82,2%), drinker (53,2%) and drug abuse (42%). Most of the students recognized that they took the risks behaviour to get pleasure with their peers. Information from the teachers indicated that most problem of male students were smoking and drug and substance abuse; while sexuality including unwanted pregnancies were reproductive problems of many female students. Therefore, It is recommended to enhance understanding of the adolescents about risks of unhealthy behaviour through continuing reproductive health education, both in school and out of school. Policy support to create positive social environment and adolescents friendly is also suggested.

Keywords: reproductive health, behaviour, early adolescents, pantura line

Procedia PDF Downloads 289
1942 Functional Slow Release of Encapsulated Ibuprofen in Cross-linked Gellan Gum Hydrogel for Tissue Engineering Application

Authors: Nor Jannah Mohd Sebri, Khairul Anuar Mat Amin

Abstract:

Dication cross-linked gellan gum hydrogel loaded with Ibuprofen with excellent mechanical properties had been synthesized as potential candidate for non-toxic biocompatible polymer material in tissue engineering. The gellan gum hydrogel with 5% Ibuprofen had produced a slow release profile with total drug release time of 25 hours as a resulting low swelling value recorded at 22+0.5%. Its compressive strength, 200.13+21 kPa was highest of all other hydrogel ratio of 0.5% and 1.0% Ibuprofen incorporation. Young’s Modulus of the hydrogel with 5% Ibuprofen was recorded at 1.8+0.01 MPa, indicating good gel strength in which it is capable of withstanding a fair amount of subjected force during topical wound dressing application. Excellent mechanical properties, together with slow release profile, make the ibuprofen-loaded hydrogel a prospect candidate as biocompatible extracellular matrices in wound management.

Keywords: gellan gum, ibuprofen, slow drug release, hydrogel

Procedia PDF Downloads 400
1941 Biodegradable Polymer Composites of MOF-5 for Efficient and Sustained Delivery of Cephalexin and Metronidazole

Authors: Anoff Anim, Lila A. M. Mahmoud, Maria Katsikogianni, Sanjit Nayak

Abstract:

Sustained and controlled delivery of antimicrobial drugs have been largely studied recently using metal organic frameworks (MOFs)and different polymers. However, much attention has not been given to combining both MOFs and biodegradable polymers, which would be a good strategy in providing a sustained gradual release of the drugs. Herein, we report a comparative study of the sustained and controlled release of widely used antibacterial drugs, cephalexin and metronidazole, from zinc-based MOF-5 incorporated in biodegradable polycaprolactone (PCL) and poly-lactic glycolic acid (PLGA) membranes. Cephalexin and metronidazole were separately incorporated in MOF-5 post-synthetically, followed by their integration into biodegradable PLGA and PCL membranes. The pristine MOF-5 and the loaded MOFs were thoroughly characterized by FT-IR, SEM, TGA and PXRD. Drug release studies were carried out to assess the release rate of the drugs in PBS and distilled water for up to 48 hours using UV-Vis Spectroscopy. Four bacterial strains from both the Gram-positive and Gram-negative types, Staphylococus aureus, Staphylococuss epidermidis, Escherichia coli, Acinetobacter baumanii, were tested against the pristine MOF, pure drugs, loaded MOFs and the drug-loaded MOF-polymer composites. Metronidazole-loaded MOF-5 composite of PLGA (PLGA-Met@MOF-5) was found to show highest efficiency to inhibit the growth of S. epidermidis compared to the other bacteria strains while maintaining a sustained minimum inhibitory concentration (MIC). This study demonstrates that the combination of biodegradable MOF-polymer composites can provide an efficient platform for sustained and controlled release of antimicrobial drugs and can be a potential strategy to integrate them in biomedical devices.

Keywords: antimicrobial resistance, biodegradable polymers, cephalexin, drug release metronidazole, MOF-5, PCL, PLGA

Procedia PDF Downloads 139
1940 Double Liposomes Based Dual Drug Delivery System for Effective Eradication of Helicobacter pylori

Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

Abstract:

The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

Procedia PDF Downloads 207
1939 Patent Protection for AI Innovations in Pharmaceutical Products

Authors: Nerella Srinivas

Abstract:

This study explores the significance of patent protection for artificial intelligence (AI) innovations in the pharmaceutical sector, emphasizing applications in drug discovery, personalized medicine, and clinical trial optimization. The challenges of patenting AI-driven inventions are outlined, focusing on the classification of algorithms as abstract ideas, meeting the non-obviousness standard, and issues around defining inventorship. The methodology includes examining case studies and existing patents, with an emphasis on how companies like Benevolent AI and Insilico Medicine have successfully secured patent rights. Findings demonstrate that a strategic approach to patent protection is essential, with particular attention to showcasing AI’s technical contributions to pharmaceutical advancements. Conclusively, the study underscores the critical role of understanding patent law and innovation strategies in leveraging intellectual property rights in the rapidly advancing field of AI-driven pharmaceuticals.

Keywords: artificial intelligence, pharmaceutical industry, patent protection, drug discovery, personalized medicine, clinical trials, intellectual property, non-obviousness

Procedia PDF Downloads 12
1938 Formulation and Characterization of Antimicrobial Chewing Gum Delivery of Some Herbal Extracts for Treatment of Periodontal Diseases

Authors: Reenu Yadav, Vidhi Guha, Udit N. Soni, Jay Ram Patel

Abstract:

Chewing gums are mobile novel drug delivery systems, with a potential for administering drugs either for local action or for systemic absorption via the buccal route. An antimicrobial chewing gum delivery system of the methanolic extracts of Beatea monosperma (barks and twigs), Cordia obliqua (leaves and seeds) and Cuminun cyminum (seeds) against periodontal diseases caused by some oral pathogens, was designed and characterized on various parameters.The results of the study support the traditional application of the plants and suggest, plant extracts possess compounds with antimicrobial properties that can be used as potential antimicrobial agents and gums can be a good carrier of herbal extracts. Developed formulation will cure/protect from various periodontal diseases. Further development and evaluations chewing gums including the isolated compounds on the commercial scale and their clinical and toxicological studies are the future challenges.

Keywords: periodontal diseases, herbal chewing gum, herbal extracts, novel drug delivery systems

Procedia PDF Downloads 394
1937 Case Report: A Case of Confusion with Review of Sedative-Hypnotic Alprazolam Use

Authors: Agnes Simone

Abstract:

A 52-year-old male with unknown psychiatric and medical history was brought to the Psychiatric Emergency Room by ambulance directly from jail. He had been detained for three weeks for possession of a firearm while intoxicated. On initial evaluation, the patient was unable to provide a reliable history. He presented with odd jerking movements of his extremities and catatonic features, including mutism and stupor. His vital signs were stable. Patient was transferred to the medical emergency department for work-up of altered mental status. Due to suspicion for opioid overdose, the patient was given naloxone (Narcan) with no improvement. Laboratory work-up included complete blood count, comprehensive metabolic panel, thyroid stimulating hormone, vitamin B12, folate, magnesium, rapid plasma reagin, HIV, blood alcohol level, aspirin, and Tylenol blood levels, urine drug screen, and urinalysis, which were all negative. CT head and chest X-Ray were also negative. With this negative work-up, the medical team concluded there was no organic etiology and requested inpatient psychiatric admission. Upon re-evaluation by psychiatry, it was evident that the patient continued to have an altered mental status. Of note, the medical team did not include substance withdrawal in the differential diagnosis due to stable vital signs and a negative urine drug screen. The psychiatry team decided to check California's prescription drug monitoring program (CURES) and discovered that the patient was prescribed benzodiazepine alprazolam (Xanax) 2mg BID, a sedative-hypnotic, and hydrocodone/acetaminophen 10mg/325mg (Norco) QID, an opioid. After a thorough chart review, his daughter's contact information was found, and she confirmed his benzodiazepine and opioid use, with recent escalation and misuse. It was determined that the patient was experiencing alprazolam withdrawal, given this collateral information, his current symptoms, negative urine drug screen, and recent abrupt discontinuation of medications while incarcerated. After admission to the medical unit and two doses of alprazolam 2mg, the patient's mental status, alertness, and orientation improved, but he had no memory of the events that led to his hospitalization. He was discharged with a limited supply of alprazolam and a close follow-up to arrange a taper. Accompanying this case report, a qualitative review of presentations with alprazolam withdrawal was completed. This case and the review highlights: (1) Alprazolam withdrawal can occur at low doses and within just one week of use. (2) Alprazolam withdrawal can present without any vital sign instability. (3) Alprazolam withdrawal does not respond to short-acting benzodiazepines but does respond to certain long-acting benzodiazepines due to its unique chemical structure. (4) Alprazolam withdrawal is distinct from and more severe than other benzodiazepine withdrawals. This case highlights (1) the importance of physician utilization of drug-monitoring programs. This case, in particular, relied on California's drug monitoring program. (2) The importance of obtaining collateral information, especially in cases in which the patient is unable to provide a reliable history. (3) The importance of including substance intoxication and withdrawal in the differential diagnosis even when there is a negative urine drug screen. Toxidrome of withdrawal can be delayed. (4) The importance of discussing addiction and withdrawal risks of medications with patients.

Keywords: addiction risk of benzodiazepines, alprazolam withdrawal, altered mental status, benzodiazepines, drug monitoring programs, sedative-hypnotics, substance use disorder

Procedia PDF Downloads 138