Search results for: computer-aided drug design

Authors: Rajasekhar Reddy Poonuru, Anusha Parnem

Abstract:

Purpose: To formulate proliposome powder of agomelatine, an antipsychotic drug, and to evaluate physicochemical, in vitro characters and effect of surface charge on ex vivo intestinal permeation. Methods: Film deposition technique was employed to develop proliposomal powders of agomelatin with varying molar ratios of lipid Hydro Soy PC L-α-phosphatidylcholine (HSPC) and cholesterol with fixed sum of drug. With the aim to derive free flowing and stable proliposome powder, fluid retention potential of various carriers was examined. Liposome formation and number of vesicles formed for per mm3 up on hydration, vesicle size, and entrapment efficiency was assessed to deduce an optimized formulation. Sodium cholate added to optimized formulation to induce surface charge on formed vesicles. Solid-state characterization (FTIR, DSC, and XRD) was performed with the intention to assess native crystalline and chemical behavior of drug. The in vitro dissolution test of optimized formulation along with pure drug was evaluated to estimate dissolution efficiency (DE) and relative dissolution rate (RDR). Effective permeability co-efficient (Peff(rat)) in rat and enhancement ratio (ER) of drug from formulation and pure drug dispersion were calculated from ex vivo permeation studies in rat ileum. Results: Proliposomal powder formulated with equimolar ratio of HSPC and cholesterol ensued in higher no. of vesicles (3.95) with 90% drug entrapment up on hydration. Neusilin UFL2 was elected as carrier because of its high fluid retention potential (4.5) and good flow properties. Proliposome powder exhibited augmentation in DE (60.3 ±3.34) and RDR (21.2±01.02) of agomelation over pure drug. Solid state characterization studies demonstrated the transformation of native crystalline form of drug to amorphous and/or molecular state, which was in correlation with results obtained from in vitro dissolution test. The elevated Peff(rat) of 46.5×10-4 cm/sec and ER of 2.65 of drug from charge induced proliposome formulation with respect to pure drug dispersion was assessed from ex vivo intestinal permeation studies executed in ileum of wistar rats. Conclusion: Improved physicochemical characters and ex vivo intestinal permeation of drug from charge induced proliposome powder with Neusilin UFL2 unravels the potentiality of this system in enhancing oral delivery of agomelatin.

Keywords: agomelatin, proliposome, sodium cholate, neusilin

Procedia PDF Downloads 101

Authors: Gayathri Vijayakumar, Preethi Baskaran

Abstract:

The effluents that are let down by the industries mix with the water bodies and drastically affect the aquatic life, which leads to pollution and bio magnifications. Effluents mostly contain chemicals, heavy metals etc., and cause toxicity to the environment. The pharmaceutical industries too contribute. The by-products and other unwanted waste are discharged without any treatment; these causes DNA damage and affect behavior of aquatic life. The study was conducted on koi carp (Cyprinus carpio) the ornamental variety of common carp. A two week long study was conducted on them using common anti-depressant drug (Diazepam) in various concentrations. These drugs are known to cause behavioral damage and organ malfunctions (muscle twitch). The histopathological study conducted showed permanent muscle twitching and lesions in the fish samples studied. The sociability was also affected in the span of 14 days. Higher concentrations of this drug showed severe damage in the muscle structures. Thus, this drug can cause adverse effects on marine ecosystem and eventually cause bio magnification of drug by running through the food chain.

Keywords: pollution, toxicity, bio-magnifications, koi carp, muscle twitch, diazepam, histopathology

Procedia PDF Downloads 64

Authors: Nagat M. Saeed, Mabruka S. Elashheb, Fatma M. Ben Rabaha, Aisha M Edrah

Abstract:

The aim of the study was to determine the type and pattern of antibiotic susceptibility of the pathogenic microorganisms causing chronic suppurative otitis media (CSOM), which could lead to better therapeutic decisions and consequently avoidance of appearance of resistance to specific antibiotics. Most frequently isolated agents were Pseudomonas aeruginosa 28.5%; followed by Staphylococcus aureus 18.2%; proteus mirabilis 13.9%; Providencia stuartti 6.7%; Bacteroides melaninogenicus, Aspergillus sp., candida sp., 4.2% each; and other microorganisms were represented in 3-0.2%. Drug sensitivities pattern of Pseudomonas aeruginosa showed that ciprofloxacin was active against the majority of isolates (93.9%) followed by ceftazidime 86.2%, amikacin 76.2% and gentamicin 40.8%. However, Staphylococcus aureus isolates were resistant to penicillin 72.7%, erythromycin 28.6%, cephalothin 18.2%, cloxacillin 8.3% and ciprofloxacin was active against 96.2% of isolates. The resistance pattern of proteus mirabilis was 55.6% to ampicillin, 47.1% to carbencillin, 29.4% to cephalothin, 14.3% to gentamicin and 4.8% to amikacin while 100% were sensitive to ciprofloxacin. We conclude that ciprofloxacin is the best drug of choice in the treatment of CSOM caused by the common microorganisms.

Keywords: otitis media, chronic suppurative otitis media (CSOM), microorganisms, drug sensitivity

Procedia PDF Downloads 313

Authors: Arianna Zhu, Thomas Bakupog

Abstract:

Taxol (generic name paclitaxel) is an antineoplastic drug used to treat breast, lung, and ovarian cancer. It performs exceptionally well against a wide variety of tumors, including B16 melanoma, L1210 and P388 leukemias, MX-1 mammary tumors, and CX-1 colon tumor xenografts. However, despite taxol’s efficacy in antitumor activity, its aqueous solubility is extremely poor, decreasing its bioavailability and making it difficult for the body to absorb. The objective of this study is to improve the solubility of taxol, thus increasing the bioavailability of the drug in preventing cancer. By modifying the structure of taxol, four novel taxol derivatives were created with improved solubilities. Two of the derivatives were given an additional hydrogen donor and acceptor and thus showed a pronounced positive change in solubility. The results of this work solve the issue of taxol’s inadequate solubility and show potential in increasing the absorption of the drug.

Keywords: Taxol, Solubility, improving bioavailability, logP

Procedia PDF Downloads 31

Authors: Paresh Patel, Harshit Patel

Abstract:

Superficial fungal skin infection is among the most common skin disease. The drug administration through skin has received attention due to several advantages: Avoidance of significant pre-systemic metabolism, drug levels within the therapeutic window, drugs with short biological half-lives, decreased side effects, the non-invasive character, and very high acceptance.

Keywords: transdermal spray, ketoconazole, Eudragit® RLPO, therapeutic window

Procedia PDF Downloads 357

Authors: Yuan Yang, Mickey Lam

Abstract:

Oral dissolvable films have been considered as a unique alternative approach to conventional oral dosage forms. The films could be administrated via the gastrointestinal tract as conventional dosages or through sublingual/buccal mucosa membranes, which could enhance drug bioavailability by avoiding the first-pass effect and improving permeability due to high blood flow and lymphatic circulation. This work has described a state-of-art technic using nano-emulsion/nano-suspension as a precursor for the film to enhance the bioavailability of BCS class II drugs. The drug molecules are consequentially processed through the emulsification, gelation, and film-casting processes. The gelation process is critical to stabilizing the nano-emulsion for the film-casting as well as controlling the drug release process. Furthermore, the size of the nanoparticle on the film has a strong correlation with the size of the micelles in the precursor and the condition of the gelation process. It has been discovered that nanoparticle from 200 nm to 300 nm has shown the highest permeability for sublingual administration. In one example shown in work, the bioavailability of a low solubilize drug has been increased from 10% to 24% via sublingual administration of the film. The increasing of the bioavailability was thought to be associated with the enhancement of the diffusion process of the drug in the saliva layer above the mucosa membrane and the fact that the presents of the emulsifier help lose the rigid junction of the mucosa cells.

Keywords: oral dissolvable film, nano-suspension, nano-emulsion, bioavailability

Procedia PDF Downloads 142

Authors: Nadia A. Mohamed, Zakaria El-Khayat, Wagdy K. B. Khalil, Mehrez E. El-Naggar

Abstract:

Drug nephrotoxicity is still a problem for patients who have taken drugs for elongated periods or permanently. Ultrasound-assisted sol−gel method was used to prepare hollow structured poroussilica nanoemulsion loaded with sodium salicylate as a model drug. The work was extended to achieve the target of the current work via investigating the protective role of this nanoemulsion model as anti-inflammatory drug or ginger for its antioxidant effect against cisplatin-induced nephrotoxicity in male albino rats. The results clarify that the nanoemulsion model was synthesized using ultrasonic assisted with small size and well stabilization as proved by TEM and DLS analysis. Additionally, blood urea nitrogen (BUN), Serum creatinine (SC) and Urinary total protein (UTP) were increased, and the level of creatinine clearance (Crcl) was decreased. All those were met with disorders in oxidative stress and downregulation in the expression of the nephrin gene. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with silica nanoparticles loaded sodium salicylate (Si-Sc-NPs), ginger or both. Conclusions oil/water nanoemulsion of (Si-Sc NPs) and ginger showed a protective and promising preventive strategy against nephrotoxicity due to their antioxidant and anti-inflammatory effects, and that offers a new approach in attenuating drug induced nephrotoxicity.

Keywords: sodium salicylate nanoencapsulation, nephrin mRNA, drug nephrotoxicity, cisplatin, experimental rats

Procedia PDF Downloads 168

Authors: Umme Hani, H. G. Shivakumar, M. D. Younus Pasha

Abstract:

The purpose of this work was to design and optimize a novel vaginal drug delivery system for more effective treatment against vaginal candidiasis. To achieve a better therapeutic efficacy and patient compliance in the treatment for vaginal candidiasis, herbal antifungal agent Curcumin which is 2.5 fold more potent than fluconazole at inhibiting the adhesion of candida albicans has been formulated in a bio-adhesive vaginal film. Curcumin was formulated in bio-adhesive film formulations that could be retained in the vagina for prolonged intervals. The polymeric films were prepared by solvent evaporation and optimized for various physicodynamic and aesthetic properties. Curcumin HPβCD (Hydroxypropyl β Cyclodextrin) was first developed to increase the solubility of curcumin. The formation of the Curcumin HPβCD complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and FT-IR and evaluated for its solubility. Curcumin HPβCD complex was formulated in a bio-adhesive film using hydroxypropyl methyl cellulose (HPMC) and Carbopol 934P and characterized. DSC and FT-IR data of Curcumin HPβCD indicate there was complex formation between the drug and HPβCD. The little moisture content (8.02±0.34% w/w) was present in the film, which helps them to remain stable and kept them from being completely dry and brittle. The mechanical properties, tensile strength, and percentage elongation at break reveal that the formulations were found to be soft and tough. The films showed good peelability, relatively good swelling index, and moderate tensile strength and retained vaginal mucosa up to 8 h. The developed Curcumin vaginal film could be a promising safe herbal medication and can ensure longer residence at the vagina and provide an efficient therapy for vaginal candidiasis.

Keywords: curcumin, curcumin-HPβCD complex, bio-adhesive vaginal film, vaginal candidiasis, 23 factorial design

Procedia PDF Downloads 353

Authors: Rui Sang, Fei Deng, Alexander Engel, Ewa M. Goldys, Wei Deng

Abstract:

In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU), and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells’ growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

Keywords: pdt, targeted lipid-polymer nanoparticles, verteporfin, colorectal cancer

Procedia PDF Downloads 48

Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

Abstract:

Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

Procedia PDF Downloads 336

Authors: Mazita Mohd Diah, Anton V. Dolzhenko, Tin Wui Wong

Abstract:

Nanoparticles, being small with a large specific surface area, increase solubility, enhance bioavailability, improve controlled release and enable precision targeting of the entrapped compounds. In this study, chitosan as polymeric permeation enhancer was conjugated to a polar pro-drug, carboxymethyl-5-fluorouracil (CMFU) to increase the skin drug permeation. Chitosan-CMFU conjugate was synthesized using chemical conjugation process through succinate linker. It was then transformed into nanoparticles via spray drying method. The conjugation was elucidated using Fourier Transform Infrared and Proton Nuclear Magnetic Resonance techniques. The nanoparticle size, size distribution, zeta potential, drug content, skin permeation and retention profiles were characterized. The conjugation was denoted using 1H NMR by new peaks at signal δ = 4.184 ppm (singlet, 2H for CH2) and 7.676-7.688 ppm (doublet, 1H for C6) attributed to CMFU in chitosan-CMFU NMR spectrum. The nanoparticles had profiles of particle size: 93.97 ±35.11 nm, polydispersity index: 0.40 ± 0.14, zeta potential: +18.25 ±2.95 mV and drug content: 6.20 ± 1.98 % w/w. Almost 80 % w/w CMFU in the form of nanoparticles permeated through the skin in 24 hours and close to 50 % w/w permeation occurred in first 1-2 hours. Without conjugation to chitosan and nanoparticulation, less than 40 % w/w CMFU permeated through the skin in 24 hours. The skin drug retention likewise was higher with chitosan-CMFU nanoparticles (15.34 ± 5.82 % w/w) than CMFU (2.24 ± 0.57 % w/w). CMFU, through conjugation with chitosan permeation enhancer and processed in nanogeometry, had its skin permeation and retention degree promoted.

Keywords: carboxymethyl-5-fluorouracil, chitosan, conjugate, skin permeation, skin retention

Procedia PDF Downloads 332

Authors: Thomas Geninatti, Bruno Giacomo, Alessandro Grattoni

Abstract:

Nanofluidic devices have been investigated for over a decade as promising platforms for the controlled release of therapeutics. The nanochannel drug delivery system (nDS), a membrane fabricated with high precision silicon techniques, capable of zero-order release of drugs by exploiting diffusion transport at the nanoscale originated from the interactions between molecules with nanochannel surfaces, showed the flexibility of the sustained release in vitro and in vivo, over periods of time ranging from weeks to months. To improve the implantable bio nanotechnology, in order to create a system that possesses the key features for achieve the suitable release of therapeutics, the next generation of nDS has been created. Platinum electrodes are integrated by e-beam deposition onto both surfaces of the membrane allowing low voltage (<2 V) and active temporal control of drug release through modulation of electrostatic potentials at the inlet and outlet of the membrane’s fluidic channels. Hence, a tunable administration of drugs is ensured from the nanochannel drug delivery system. The membrane will be incorporated into a peek implantable capsule, which will include drug reservoir, control hardware and RF system to allow suitable therapeutic regimens in real-time. Therefore, this new nanotechnology offers tremendous potential solutions to manage chronic disease such as cancer, heart disease, circadian dysfunction, pain and stress.

Keywords: nanochannel membrane, drug delivery, tunable release, personalized administration, nanoscale transport, biomems

Procedia PDF Downloads 280

Authors: Lian Zeng

Abstract:

Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

Procedia PDF Downloads 69

Authors: Priya Patel, Paresh Patel, Mihir Raval

Abstract:

Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.

Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability

Procedia PDF Downloads 396

Authors: Jacob Green, Cecilia Cabrera, Maximilian Jakobs, Andrea Dimitracopoulos, Mark van der Wilk, Ryan Greenhalgh

Abstract:

Predicting drug properties is key in drug discovery to enable de-risking of assets before expensive clinical trials and to find highly active compounds faster. Interest from the machine learning community has led to the release of a variety of benchmark datasets and proposed methods. However, it remains unclear for practitioners which method or approach is most suitable, as different papers benchmark on different datasets and methods, leading to varying conclusions that are not easily compared. Our large-scale empirical study links together numerous earlier works on different datasets and methods, thus offering a comprehensive overview of the existing property classes, datasets, and their interactions with different methods. We emphasise the importance of uncertainty quantification and the time and, therefore, cost of applying these methods in the drug development decision-making cycle. To the best of the author's knowledge, it has been observed that the optimal approach varies depending on the dataset and that engineered features with classical machine learning methods often outperform deep learning. Specifically, QSAR datasets are typically best analysed with classical methods such as Gaussian Processes, while ADMET datasets are sometimes better described by Trees or deep learning methods such as Graph Neural Networks or language models. Our work highlights that practitioners do not yet have a straightforward, black-box procedure to rely on and sets a precedent for creating practitioner-relevant benchmarks. Deep learning approaches must be proven on these benchmarks to become the practical method of choice in drug property prediction.

Keywords: activity (QSAR), ADMET, classical methods, drug property prediction, empirical study, machine learning

Procedia PDF Downloads 44

Authors: Pooja Mongia Raj, Rakesh Raj, Alpana Ram

Abstract:

Background: The use of multiparticulate drug delivery systems in preference to single unit dosage forms for colon targeting purposes dates back to 1985 when Hardy and co-workers showed that multiparticulate systems enabled the drug to reach the colon quickly and were retained in the ascending colon for a relatively long period of time. Methods: Site-specific colonic drug delivery system (nanoparticles) of 5-ASA were prepared and coated with pH sensitive polymer. Chitosan nanoparticles (CTNP) bearing 5-Amino salicylic acid (5-ASA) were prepared, by ionotropic gelation method. Nanoparticulate dosage form consisting of a hydrophobic core enteric coated with pH-dependent polymer Eudragit S-100 by solvent evaporation method, for the effective delivery of drug to the colon for treatment of ulcerative colitis. Results: The mean diameter of CTNP and ECTNP formulations were 159 and 661 nm, respectively. Also optimum value of polydispersity index was found to be 0.249 [count rate (kcps) was 251.2] and 0.170 [count rate (kcps) was 173.9] was obtained for both the formulations respectively. Conclusion: CTNP and Eudragit chitosan nanoparticles (ECTNP) was characterized for shape and surface morphology by scanning electron microscopy (SEM) appeared to be spherical in shape. The in vitro drug release was investigated using USP dissolution test apparatus in different simulated GIT fluids showed promising release. In vivo experiments are in further proceeding for fruitful results.

Keywords: colon targeting, nanoparticles, polymer, 5-amino salicylic acid, edragit

Procedia PDF Downloads 468

Authors: Rady A., Elsheshai A., Elsawy M., Nagui R.

Abstract:

Background and Aim: Metabolic syndrome affect around 20% of general population , authors have incriminated antipsychotics as serious risk factor that may provoke such derangement. The aim of our study is to assess metabolic syndrome in patients presenting psychotic features (delusions and hallucinations) whether schizophrenia or mood disorder and compare results in terms of drug naïf, on medication and healthy control. Subjects and Methods: The study recruited 40 schizophrenic patients, half of them drug naïf and the other half on antipsychotics, 40 patients with mood disorder with psychotic features, half of them drug naïf and the other half on medication, 20 healthy control. Exclusion criteria were put in order to exclude patients having already endocrine or metabolic disorders that my interfere with results obtain to minimize confusion bias. Metabolic syndrome assessed by measuring parameters including weight, body mass index, waist circumference, triglyceride level, HDL, fasting glucose, fasting insulin and insulin resistance Results: No difference was found when comparing drug naïf to those on medication in both schizophrenic and psychotic mood disorder arms, schizophrenic patients whether on medication or drug naïf should difference with control group for fasting glucose, schizophrenic patients on medication also showed difference in insulin resistance compared to control group. On the other hand, patients with psychotic mood disorder whether drug naïf or on medication showed difference from control group for fasting insulin level. Those on medication also differed from control for insulin resistance Conclusion: Our study didn’t reveal difference in metabolic syndrome among patients with psychotic features whether on medication or drug naïf. Only patients with Psychotic features on medication showed insulin resistance. Schizophrenic patients drug naïf or on medication tend to show higher fasting glucose while psychotic mood disorder whether drug naïf or on medication tend to show higher fasting insulin. This study suggest that presence of psychotic features themselves regardless being on medication or not carries a risk for insulin resistance and metabolic syndrome. Limitation: This study is limited by number of participants and larger numbers in future studies should be included in order to extrapolate results. Cohort longitudinal studies are needed in order to evaluate such hypothesis.

Keywords: schizophrenia, metabolic syndrome, psychosis, insulin, resistance

Procedia PDF Downloads 508

Authors: Ubaka Chukwuemeka Michael, Ukwe Chinwe Victoria

Abstract:

Background: The use of antipsychotic monotherapy remains the standard for schizophrenic disorders so also a prescription switch from older typical to newer atypical classes of antipsychotics on the basis of better efficacy and tolerability. However, surveys on the quality of antipsychotic drug use and substitution in developing countries are very scarce. This study was intended to evaluate quality and factors that drive the prescription and substitution of antipsychotic drugs among schizophrenic patients visiting a regional psychiatric hospital. Methods: Case files of patients visiting a federal government funded Neuropsychiatric Hospital between July 2012 and July 2014 were systematically retrieved. Patient demographic characteristics, clinical details and drug management data were collected and subjected to descriptive and inferential data analysis to determine quality and predictors of utilization. Results: Of the 600 case files used, there were more male patients (55.3%) with an overall mean age of 33.7±14.4 years. Typical antipsychotic agents accounted for over 85% of prescriptions, with majority of the patients receiving more than 2 drugs in at least a visit (80.9%). Fluphenazine (25.2%) and Haloperidol (18.8%) were mostly given as antipsychotics for treatment initiation while Olazenpine (23.0%) and Benzhexol (18.3%) were the most currently prescribed antipsychotics. Nearly half (42%, 252/600) of these patients were switched from one class to another, with 34.5% (207/600) of them switched from typical to atypical drug classes. No demographic or clinical factors influenced drug substitutions but a younger age and being married influenced being prescribed a polypharmacy regimen (more than 2 drugs) and an injectable antipsychotic agent. Conclusion: The prevalence of antipsychotic polypharmacy and use of typical agents among these patients was high. However, only age and marital status affected the quality of antipsychotic prescriptions among these patients.

Keywords: antipsychotics, drug substitution, pharmacoepidemiology, polypharmacy

Procedia PDF Downloads 440

Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.

Abstract:

Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.

Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring

Procedia PDF Downloads 48

Authors: Yogita Patil-Sen

Abstract:

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have become increasingly important materials for separation of specific bio-molecules, drug delivery vehicle, contrast agent for MRI and magnetic hyperthermia for cancer therapy. Hyperthermia is emerging as an alternative cancer treatment to the conventional radio- and chemo-therapy, which have harmful side effects. When subjected to an alternating magnetic field, the magnetic energy of SPIONs is converted into thermal energy due to movement of particles. The ability of SPIONs to generate heat and potentially kill cancerous cells, which are more susceptible than the normal cells to temperatures higher than 41 °C forms the basis of hyerpthermia treatement. The amount of heat generated depends upon the magnetic properties of SPIONs which in turn is affected by their properties such as size and shape. One of the main problems associated with SPIONs is particle aggregation which limits their employability in in vivo drug delivery applications and hyperthermia cancer treatments. Coating the iron oxide core with thermally responsive lipid based nanostructures tend to overcome the issue of aggregation as well as improve biocompatibility and can enhance drug loading efficiency. Herein we report suitability of SPIONs and silica coated core-shell SPIONs, which are further, coated with various lipids for drug delivery and magnetic hyperthermia applications. The synthesis of nanoparticles is carried out using the established methods reported in the literature with some modifications. The nanoparticles are characterised using Infrared spectroscopy (IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM). The heating ability of nanoparticles is tested under alternating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of alternating magnetic field. The results suggest that the nanoparticles exhibit superparamagnetic behaviour, although coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the alternating magnetic field. Thus, the results demonstrate that lipid coated SPIONs exhibit potential as drug delivery vehicles for magnetic hyperthermia based cancer therapy.

Keywords: drug delivery, hyperthermia, lipids, superparamagnetic iron oxide nanoparticles (SPIONS)

Procedia PDF Downloads 204

Authors: Wantana Amatariyakul, Chumnong Amatariyakul

Abstract:

The research aims to examine the spread of drugs in higher education, especially amphetamine which is rapidly increasing in Thai society, its causes and effects, including the sociological perspective, in order to explain, prevent, control, and solve the problems. The students who participated in this research are regular students of Rajamangala University of Technology Isan, Khon Kaen Campus. The data were collected using questionnaires, group discussions, and in-depth interviews. The quantity data were analyzed using frequency, percentage, mean and standard deviation and using content analysis to analyzed quality data. The result of the study showed that the students had the results of examination on level of knowledge and understanding on drug abuse projected that the majority of sample group attained their knowledge on drug abuse respectively. Despite their uncertainty, the majority of samples presumed that amphetamine, marijuana and grathom (Mitragyna Speciosa Korth) would most likely be abused. The reason for first drug abuse is because they want to try and their friends convince them, as well as, they want to relax or solve the problems in life, respectively. The bad effects appearing to the drug addicts shows that their health deteriorates or worsens, as well as, they not only lose their money but also face with worse mental states. The reasons that respondents tried to avoid using drugs or refused drugs offered by friends were: not wanting to disappoint or upset their family members, fear of rejection by family members, afraid of being arrested by the police, afraid of losing their educational opportunity and ruining their future respectively. Students therefore defended themselves against drug addiction by refusing to try all drugs. Besides this, the knowledge about the danger and the harm of drugs persuaded them to stay away from drugs.

Keywords: drugs, higher education, drug addiction, spread of drugs

Procedia PDF Downloads 291

Authors: Afzal Hussain, Mohammad A. Altamimi, Syed Sarim Imam, Mudassar Shahid, Osamah Abdulrahman Alnemer

Abstract:

Exhaustive application of sulfamethoxazole (SUX) became as a global threat for human health due to water contamination through diverse sources. The addressed combined application of Hansen solubility (HSPiP software) parameters and Quality by Design tool for developing various green nanoemulsions. HSPiP program assisted to screen suitable excipients based on Hansen solubility parameters and experimental solubility data. Various green nanoemulsions were prepared and characterized for globular size, size distribution, zeta potential, and removal efficiency. Design Expert (DoE) software further helped to identify critical factors responsible to have direct impact on percent removal efficiency, size, and viscosity. Morphological investigation was visualized under transmission electron microscopy (TEM). Finally, the treated was studied to negate the presence of the tested drug employing ICP-OES (inductively coupled plasma optical emission microscopy) technique and HPLC (high performance liquid chromatography). Results showed that HSPiP predicted biocompatible lipid, safe surfactant (lecithin), and propylene glycol (PG). Experimental solubility of the drug in the predicted excipients were quite convincing and vindicated. Various green nanoemulsions were fabricated, and these were evaluated for in vitro findings. Globular size (100-300 nm), PDI (0.1-0.5), zeta potential (~ 25 mV), and removal efficiency (%RE = 70-98%) were found to be in acceptable range for deciding input factors with level in DoE. Experimental design tool assisted to identify the most critical variables controlling %RE and optimized content of nanoemulsion under set constraints. Dispersion time was varied from 5-30 min. Finally, ICP-OES and HPLC techniques corroborated the absence of SUX in the treated water. Thus, the strategy is simple, economic, selective, and efficient.

Keywords: quality by design, sulfamethoxazole, green nanoemulsion, water treatment, icp-oes, hansen program (hspip software

Procedia PDF Downloads 48

Authors: Mohammad Aziz Shah Mohamed Arip, Aslina Ahmad, Fauziah Mohd Sa'ad, Samsiah Mohd Jais, Syed Sofian Syed Salim

Abstract:

This experimental study evaluates the effect of using Cognitive-Behavioral Therapy (CBT) and Multidimensional Self-Concept Model (MSCM) in a drug prevention programme to increase resiliency and reduce aggression among at-risk youth in Malaysia. A number of 60 (N=60) university students who were at-risk of taking drugs were involved in this study. Participants were identified with self-rating scales, Adolescent Resilience Attitude Scale (ARAS) and Aggression Questionnaire. Based on the mean score of these instruments, the participants were divided into the treatment group, and the control group. Data were analyzed using t-test. The finding showed that the mean score of resiliency was increased in the treatment group compared to the control group. It also shows that the mean score of aggression was reduced in the treatment group compared to the control group. Drug Prevention Programme was found to help in enhancing resiliency and reducing aggression among participants in the treatment group compared to the controlled group. Implications were given regarding the preventive actions on drug abuse among youth in Malaysia.

Keywords: drug prevention programme, cognitive-behavioral therapy (CBT), multidimensional self concept model (MSCM), resiliency, aggression, at-risk youth

Procedia PDF Downloads 695

Authors: Frederick Monyepao

Abstract:

Crack cocaine first appeared on the scene in the form of cocaine freebasing in the late 1970s. Stockbrokers, investment bankers, rock stars, Hollywood elites, and a few pro athletes were regular users of the substance. As criminogenic factors associated with substance abuse began to surface, congress passed new legislation. The laws led to the increase of health coverage insurances and the expansion of hospitals. By the mid-1980s, crack use spread into America's inner cities among impoverished African Americans and Latinos. While substance abuse increased among minority communities, legislation pertaining to substance abuse evolved. The prison industry also expanded the number of cells available. A qualitative approach was taken, drawing from a range secondary sources for contextual analysis. This paper traces out the continued marginalisation and racist undertones towards minorities as perpetuated by certain drug policies. It was discovered that the new legislation on crack was instrumental in the largest incarcerations the United States ever faced. Drug offenders increased in prisons eightfold from 1986 to 2000. The paper concludes that American drug control policies are consistently irrational and ineffective when measured by levels of substance use and abuse. On the contrary, these policies have been successful as agents of social control in maintaining the stratification patterns of racial/ethnic minorities and women. To move beyond prohibition, radical law and policy reform may require a change in narratives on substance use.

Keywords: crack, drug policy, minorities, racism, substance abuse

Procedia PDF Downloads 254

Authors: Cho-Liang Chung

Abstract:

Uniform and rapid drug release are important for trauma dressing application. Low glass transition polymer system and non-woven nanofiber structures as the designs conduct rapid-release characteristics. In this study, polyvinylpyrrolidone, polysulfone, and polystyrene were dissolved in dimethylformamide to form precursor solution. These solutions were blended with vitamin C to form the electrospinning solutions. The non-woven nanofibers structures were successfully prepared using an electrospinning process. The following instruments were used to analyze the characteristics of non-woven nanofibers structures: Atomic force microscopy (AFM), Field Emission Scanning Electron Microscope (FE-SEM), and X-ray Diffraction (XRD). The AFM was used to scan the nanofibers. 3D Graphics were applied to explore the surface morphology of nanofibers. FE-SEM was used to explore the morphology of non-woven structures. XRD was used to identify crystal structures in the non-woven structures. The evolution of morphology of non-woven structures was changed dramatically in different durations, because of the moisture absorption and decreasing glass transition temperature; the non-woven nanofiber structures can be applied to uniform and rapid drug release for trauma dressing application.

Keywords: nanofibers, non-woven, electrospinning process, rapid drug releasing

Procedia PDF Downloads 110

Authors: Timea Harmath-Tánczos

Abstract:

Drug-resistant epilepsy (DRE) is defined as the persistence of seizures despite at least two syndrome-adapted antiseizure drugs (ASD) used at efficacious daily doses. About a third of patients with epilepsy suffer from drug resistance. Cognitive assessment has a crucial role in the diagnosis and clinical management of epilepsy. Previous studies have addressed the clinical targets and indications for measuring neuropsychological functions; best to our knowledge, no studies have examined it in a Hungarian therapy-resistant population. To fill this gap, we investigated the Hungarian diagnostic protocol between 18 and 65 years of age. This study aimed to describe and analyze neuropsychological functions in patients with drug-resistant epilepsy and identify factors associated with neuropsychology deficits. We perform a prospective case-control study comparing neuropsychological performances in 50 adult patients and 50 healthy individuals between March 2023 and July 2023. Neuropsychological functions were examined in both patients and controls using a full set of specific tests (general performance level, motor functions, attention, executive facts., verbal and visual memory, language, and visual-spatial functions). Potential risk factors for neuropsychological deficit were assessed in the patient group using a multivariate analysis. The two groups did not differ in age, sex, dominant hand and level of education. Compared with the control group, patients with drug-resistant epilepsy showed worse performance on motor functions and visuospatial memory, sustained attention, inhibition and verbal memory. Neuropsychological deficits could therefore be systematically detected in patients with drug-resistant epilepsy in order to provide neuropsychological therapy and improve quality of life. The analysis of the classical and complex indices of the special neuropsychological tasks presented in the presentation can help in the investigation of normal and disrupted memory and executive functions in the DRE.

Keywords: drug-resistant epilepsy, Hungarian diagnostic protocol, memory, executive functions, cognitive neuropsychology

Procedia PDF Downloads 45

Authors: Ermias A. Tegegn, Million Meshesha

Abstract:

Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome (HIV/AIDS) is a major cause of death for most African countries. Ethiopia is one of the seriously affected countries in sub Saharan Africa. Previously in Ethiopia, having HIV/AIDS was almost equivalent to a death sentence. With the introduction of Antiretroviral Therapy (ART), HIV/AIDS has become chronic, but manageable disease. The study focused on a data mining technique to predict future living status of HIV/AIDS patients at the time of drug regimen change when the patients become toxic to the currently taking ART drug combination. The data is taken from University of Gondar Hospital ART program database. Hybrid methodology is followed to explore the application of data mining on ART program dataset. Data cleaning, handling missing values and data transformation were used for preprocessing the data. WEKA 3.7.9 data mining tools, classification algorithms, and expertise are utilized as means to address the research problem. By using four different classification algorithms, (i.e., J48 Classifier, PART rule induction, Naïve Bayes and Neural network) and by adjusting their parameters thirty-two models were built on the pre-processed University of Gondar ART program dataset. The performances of the models were evaluated using the standard metrics of accuracy, precision, recall, and F-measure. The most effective model to predict the status of HIV patients with drug regimen substitution is pruned J48 decision tree with a classification accuracy of 98.01%. This study extracts interesting attributes such as Ever taking Cotrim, Ever taking TbRx, CD4 count, Age, Weight, and Gender so as to predict the status of drug regimen substitution. The outcome of this study can be used as an assistant tool for the clinician to help them make more appropriate drug regimen substitution. Future research directions are forwarded to come up with an applicable system in the area of the study.

Keywords: HIV drug regimen, data mining, hybrid methodology, predictive model

Procedia PDF Downloads 110

Authors: Santosh Sharma

Abstract:

Background: Drug abuse, needle sharing, and risky sexual behaviour are often compounded to increase the risk of HIV transmission. Injecting Drug Users are at the duel risk of needle sharing and risky sexual Behaviour, becoming more vulnerable to STI and HIV. Thus, studying the interface of injecting drug use and risky sexual behaviour is important to curb the pace of HIV epidemic among IDUs. The aim of this study is to determine the factor associated with HIV among injecting drug users in three states of India. Materials and methods: This paper analyzes covariates of multiplicity of risk behavior among injecting drug users. Findings are based on data from Integrated Behavioral and Biological Assessment (IBBA) round 2, 2010. IBBA collects the information of IDUs from the six districts. IDUs were selected on the criteria of those who were 18 years or older, who injected addictive substances/drugs for non-medical purposes at least once in past six month. A total of 1,979 in round 2 were interviewed in the IBBA. The study employs quantitative techniques using standard statistical tools to achieve the above objectives. All results presented in this paper are unweighted univariate measures. Results: Among IDUs, average duration of injecting drugs is 5.2 years. Mean duration between first drug use to first injecting drugs among younger IDUs, belongs to 18-24 years is 2.6 years Needle cleaning practices is common with above two-fifths reporting its every time cleaning. Needle sharing is quite prevalent especially among younger IDUs. Further, IDUs practicing needle sharing exhibit pervasive multi-partner behavior. Condom use with commercial partners is almost 81 %, whereas with intimate partner it is 39 %. Coexistence of needle sharing and unprotected sex enhances STI prevalence (6.8 %), which is further pronounced among divorced/separated/widowed (9.4 %). Conclusion: Working towards risk reduction for IDUs must deal with multiplicity of risk. Interventions should deal with covariates of risk, addressing youth, and risky sexual behavior.

Keywords: IDUs, HIV, STI, behaviour

Procedia PDF Downloads 253

Authors: Ashish Kumar Jain, Deepak Mishra

Abstract:

The objective of the present investigation was to prepare and evaluate a vesicular dual drug delivery system for effective management of mucosal ulcer. Inner encapsulating and Double liposomes were prepared by glass bead and reverse phase evaporation method respectively. The formulation consisted of inner liposomes bearing Ranitidine Bismuth Citrate (RBC) and outer liposomes encapsulating Amoxicillin trihydrate (AMOX). The optimized inner liposomes and double liposomes were extensively characterized for vesicle size, morphology, zeta potential, vesicles count, entrapment efficiency and in vitro drug release. In vitro, the double liposomes demonstrated a sustained release of AMOX and RBC viz 91.4±1.8% and 77.2±2.1% respectively at the end of 72 hr. Furthermore binding specificity and targeting propensity toward H. pylori (SKP-56) was confirmed by agglutination and in situ adherence assay. Reduction of the absolute alcohol induced ulcerogenic index from 3.01 ± 0.25 to 0.31 ± 0.09 and 100% H. pylori clearance rate was observed. These results suggested that double liposomes are potential vector for the development of dual drug delivery for effective treatment of H. pylori-associated peptic ulcer.

Keywords: double liposomes, H. pylori targeting, PE liposomes, glass-beads method, peptic ulcers

Procedia PDF Downloads 418

Authors: Jiji Jose, R. Narayanacharyulu, Molly Mathew, Jisha Prems

Abstract:

Introduction: Lercanidipine hydrochloride (LD), an effective calcium channel blocker, widely used for the treatment of chronic stable angina and hypertension seems to be potential transdermal therapeutic system candidate, mainly due to its low oral bio availability, short half life and high first-pass metabolism. Objective: To develop transdermal therapeutic systems for LD and to evaluate its in vivo performance in rabbits. Methodology: Transdermal patches of LD were formulated using the polymer blend of eudragit RL100 (ERL) and polyvinyl pyrolidone (PVP) by casting method Propylene glycol (PG) and tween 80 were used as plasticizer and permeation enhancer respectively. The pharmaco kinetic parameters of LD after the administration of transdermal patches was compared with that of oral administration. The study was carried out in a two way crossover design in male New Zealand albino rabbits. Results: The formulation with ERL: PVP ratio 1:4 with 15% w/w PG as plasticizer and 4% w/w tween 80 as permeation enhancer showed the best drug release results. The pharmacokinetic parameters such as Cmax, tmax, mean residence time (MRT) and area under the curve (AUC 0-∞) were significantly different following transdermal administration compared to oral administration. The terminal half life of transdermally administered LD was found to similar that of oral administration. A sustained drug release over a period of 24 hrs was observed after transdermal administration. Conclusion: The fabricated transdermal delivery system have the potential to provide controlled and extended drug release, better bio availability and thus, this may improve the patient compliance.

Keywords: transdermal therapeutic system, lercanidipine hydrochloride, eudragit, skinpermeation

Procedia PDF Downloads 589