Search results for: ocular drug delivery

Authors: Kumaran Letchmanan, Shou-Cang Shen, Wai Kiong Ng

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Postoperative implant-associated infections in soft tissues and bones remain a serious complication in orthopaedic surgery, which leads to impaired healing, re-implantation, prolong hospital stay and increase cost. Drug-loaded implants with sustained release of antibiotics at the local site are current research interest to reduce the risk of post-operative infections and osteomyelitis, thus, minimize the need for follow-up care and increase patient comfort. However, the improved drug release of the drug-loaded bone cements is usually accompanied by a loss in mechanical strength, which is critical for weight-bearing bone cement. Recently, more attempts have been undertaken to develop techniques to enhance the antibiotic elution as well as preserve the mechanical properties of the bone cements. The present study investigates the potential influence of addition of mesoporous silica nanoparticles (MSN) on the in vitro drug release kinetics of gentamicin (GTMC), along with the mechanical properties of bone cements. Simplex P was formulated with MSN and loaded with GTMC by direct impregnation. Meanwhile, Simplex P with water soluble poragen (xylitol) and high loading of GTMC as well as commercial bone cement CMW Smartset GHV were used as controls. MSN-formulated bone cements are able to increase the drug release of GTMC by 3-fold with a cumulative release of more than 46% as compared with other control groups. Furthermore, a sustained release could be achieved for two months. The loaded nano-sized MSN with uniform pore channels significantly build up an effective nano-network path in the bone cement facilitates the diffusion and extended release of GTMC. Compared with formulations using xylitol and high GTMC loading, incorporation of MSN shows no detrimental effect on biomechanical properties of the bone cements as no significant changes in the mechanical properties as compared with original bone cement. After drug release for two months, the bending modulus of MSN-formulated bone cements is 4.49 ± 0.75 GPa and the compression strength is 92.7 ± 2.1 MPa (similar to the compression strength of Simplex-P: 93.0 ± 1.2 MPa). The unaffected mechanical properties of MSN-formulated bone cements was due to the unchanged microstructures of bone cement, whereby more than 98% of MSN remains in the matrix and supports the bone cement structures. In contrast, the large portions of extra voids can be observed for the formulations using xylitol and high drug loading after the drug release study, thus caused compressive strength below the ASTM F541 and ISO 5833 minimum of 70 MPa. These results demonstrate the potential applicability of MSN-functionalized poly(methyl methacrylate)-based bone cement as a highly efficient, sustained and local drug delivery system with good mechanical properties.

Keywords: antibiotics, biomechanical properties, bone cement, sustained release

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Authors: Nagasamy Venkatesh Dhandapani

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The objective of the present study was to develop sustained release oral matrix tablets of anti epileptic drug levetiracetam. The sustained release matrix tablets of levetiracetam were prepared using hydrophilic matrix hydroxypropyl methylcellulose (HPMC) as a release retarding polymer by wet granulation method. Prior to compression, FTIR studies were performed to understand the compatibility between the drug and excipients. The study revealed that there was no chemical interaction between drug and excipients used in the study. The tablets were characterized by physical and chemical parameters and results were found in acceptable limits. In vitro release study was carried out for the tablets using 0.1 N HCl for 2 hours and in phosphate buffer pH 7.4 for remaining time up to 12 hours. The effect of polymer concentration was studied. Different dissolution models were applied to drug release data in order to evaluate release mechanisms and kinetics. The drug release data fit well to zero order kinetics. Drug release mechanism was found as a complex mixture of diffusion, swelling and erosion.

Keywords: levetiracetam, sustained-release, hydrophilic matrix tablet, HPMC grade K 100 MCR, wet granulation, zero order release kinetics

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Authors: Waraporn Boonchieng, Ekkarat Boonchieng, Sivaporn Aungwattana, Decha Tamdee, Wongamporn Pinyavong

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Drug addiction represents one of the most important public health issues in both developed and developing countries. The purpose of this study was to develop a drug abuse health information in a community in Northern Thailand using developmental research design. The developmental researchers performed four phases to develop drug abuse health information, including 1) synthesizing knowledge related to drug abuse prevention and identifying the components of drug abuse health information; 2) developing the system in mobile application and website; 3) implementing drug abuse health information in the rural community; and 4) evaluating the feasibility of drug abuse health information. Data collection involved both qualitative and quantitative procedures. The qualitative data and quantitative data were analyzed using content analysis and descriptive statistics, respectively. The findings of this study showed that drug abuse health information consisted of five sections, including drug-related prevention knowledge for teens, drug-related knowledge for adults and professionals, the database for drug dependence treatment centers, self-administered questionnaires, and supportive counseling sections. First, in drug-related prevention knowledge for teens, the developmental researchers designed four infographics and animation to provide drug-related prevention knowledge, including types of illegal drugs, causes of drug abuse, consequences of drug abuse, drug abuse diagnosis and treatment, and drug abuse prevention. Second, in drug-related knowledge for adults and professionals, the developmental researchers developed many documents in a form of PDF file to provide drug-related knowledge, including types of illegal drugs, causes of drug abuse, drug abuse prevention, and relapse prevention guideline. Third, database for drug dependence treatment centers included the place, direction map, operation time, and the way for contacting all drug dependence treatment centers in Thailand. Fourth, self-administered questionnaires comprised preventive drugs behavior questionnaire, drug abuse knowledge questionnaire, the stages of change readiness and treatment eagerness to drug use scale, substance use behaviors questionnaire, tobacco use behaviors questionnaire, stress screening, and depression screening. Finally, for supportive counseling, the developmental researchers designed chatting box through which each user could write and send their concerns to counselors individually. Results from evaluation process showed that 651 participants used drug abuse health information via mobile application and website. Among all users, 48.8% were males and 51.2% were females. More than half (55.3%) were 15-20 years old and most of them (88.0%) were Buddhists. Most users reported ever getting knowledge related to drugs (86.1%), and drinking alcohol (94.2%) while some of them (6.9%) reported ever using tobacco. For satisfaction with using the drug abuse health information, more than half of users reflected that the contents of drug abuse health information were interesting (59%), up-to date (61%), and highly useful to their self-study (59%) at high level. In addition, half of them were satisfied with the design in terms of infographics (54%) and animation (51%). Thus, this drug abuse health information can be adopted to explore drug abuse situation and serves as a tool to prevent drug abuse and addiction among Thai community people.

Keywords: drug addiction, health informatics, big data, development research

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Authors: Mattia Testuzza

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Public health is a social endeavour, which involves many different actors: from extremely stratified, structured health systems to unofficial networks of people and knowledge. Health and diseases are an intertwined individual and social experiences. Both patients and health workers navigate this public space through relations of trust. Trust in healthcare goes from the personal trust between a patient and her/his doctor to the trust of both the patient and the health worker in the medical knowledge and the healthcare system. Trust it is not a given, but it is continuously negotiated, given and gained. The key to understand these essential relations of trust in health is to recognise them as a social practice, which therefore implies agency and power. In these terms, health is constantly public and made public, as trust emerges as a meaningfully political phenomenon. Trust as a power relation can be observed at play in the implementation of public health policies such as the WHO’s Directly-Observed Theraphy Short-course (DOTS), and with the increasing concern for drug-resistance that tuberculosis pose, looking at the role of trust in the healthcare delivery system and implementation of public health policies becomes significantly relevant. The ethnographic fieldwork was carried out in four months through observation of the daily practices at the National Tuberculosis Center of Nepal, and semi-structured interviews with MultiDrug-Resistant Tuberculosis (MDR-TB) patients at different stages of the treatment, their relatives, MDR-TB specialised nurses, and doctors. Throughout the research, the role which trust plays in tuberculosis treatment emerged as one fundamental ax that cuts through all the different factors intertwined with drug-resistance development, unfolding a tension between the DOTS policy, which undermines trust, and the day-to-day healthcare relations and practices which cannot function without trust. Trust also stands out as a key component of the solutions to unforeseen issues which develop from the overall uncertainty of the context - for example, political instability and extreme poverty - in which tuberculosis treatment is carried out in Nepal.

Keywords: trust, tuberculosis, drug-resistance, politics of health

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Authors: Rajender Singh, Nidhi Sharma, Aastha Chauhan, Meenakshi Barsaul, Jyoti Deswal, Chetan Chhikara

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Introduction: Pre-eclampsia and eclampsia are hypertensive disorders of pregnancy with multisystem involvement and are common causes of morbidity and mortality in obstetrics. It is believed that changes in retinal arterioles may indicate similar changes in the placenta. Therefore, this study was undertaken to evaluate the ocular manifestations in cases of pre-eclampsia and eclampsia and to deduce any association between the retinal changes and blood pressure, the severity of disease, gravidity, proteinuria, and other lab parameters so that a better approach could be devised to ensure maternal and fetal well-being. Materials and Methods: This was a hospital-based cross-sectional study conducted over a period of one year, from April 2021 to May 2022. 350 admitted patients with diagnosed pre-eclampsia, eclampsia, and pre-eclampsia superimposed on chronic hypertension were included in the study. A pre-structured proforma was used. After taking consent and ocular history, a bedside examination to record visual acuity, pupillary size, corneal curvature, field of vision, and intraocular pressure was done. Dilated fundus examination was done with a direct and indirect ophthalmoscope. Age, parity, BP, proteinuria, platelet count, liver and kidney function tests were noted down. The patients with positive findings only were followed up after 72 hours and 6 weeks of termination of pregnancy. Results: The mean age of patients was 26.18±4.33 years (range 18-39 years).157 (44.9%) were primigravida while 193(55.1%) were multigravida.53 (15.1%) patients had eclampsia, 128(36.5%) had mild pre-eclampsia,128(36.5%) had severe pre-eclampsia and 41(11.7%) had chronic hypertension with superimposed pre-eclampsia. Retinal changes were found in 208 patients (59.42%), and grade I changes were the most common. 82(23.14%) patients had grade I changes, 75 (21.4%) had grade II changes, 41(11.71%) had grade III changes, and 11(3.14%) had serous retinal detachment/grade IV changes. 36 patients had unaided visual acuity <6/9, of these 17 had refractive error and 19(5.4%) had varying degrees of retinal changes. 3(0.85%) out of 350 patients had an abnormal field of vision in both eyes. All 3 of them had eclampsia and bilateral exudative retinal detachment. At day 4, retinopathy in 10 patients resolved, and 3 patients had improvement in visual acuity. At 6 weeks, retinopathy in all the patients resolved spontaneously except persistence of grade II changes in 23 patients with chronic hypertension with superimposed pre-eclampsia, while visual acuity and field of vision returned to normal in all patients. Pupillary size, intraocular pressure, and corneal curvature were found to be within normal limits at all times of examination. There was a statistically significant positive association between retinal changes and mean arterial pressure. The study showed a positive correlation between fundus findings and severity of disease (p value<0.05) and mean arterial pressure (p value<0.005). Primigravida had more retinal changes than multigravida patients. A significant association was found between fundus changes and thrombocytopenia and deranged liver and kidney function tests (p value<0.005). Conclusion: As the severity of pre-eclampsia and eclampsia increases, the incidence of retinopathy also increases, and it affects visual acuity and visual fields of the patients. Thus, timely ocular examination should be done in all such cases to prevent complications.

Keywords: eclampsia, hypertensive, ocular, pre-eclampsia

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Authors: Nitin Kumar

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Purpose: The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential by means of enhancing the ginsenoside (Rb1) bio-availability (BA). For more noteworthy enhancement in oral bioavailability (OBA) along with pharmacological properties, the drug carriers’ performance can be strengthened by utilizing phytosomes-loaded microspheres (PM) delivery system. Methods: For preparing the disparate phytosome complexes (F1, F2, and F3), an aqueous extract of ginseng roots (GR) along with phospholipids were reacted in disparate ratio. Considering the outcomes, F3 formulation (spray-dried) was chosen for preparing the phytosomes powder (PP), PM, and extract microspheres (EM). PM was made by means of loading of F3 into Gum Arabic (GA) in addition to maltodextrin polymer mixture, whereas EM was prepared by means of the addition of extract directly into the same polymer mixture. For investigating the neuroprotective effect (NPE) in addition to their pharmacokinetic (PK) properties, PP, PM, and EM formulations were assessed. Results: F3 formulation gave enhanced entrapment efficiency (EE) (i.e., 50.61%) along with good homogeneity of spherical shaped particle size (PS) (42.58 ± 1.4 nm) with least polydispersity index (PDI) (i.e., 0.193 ± 0.01). The sustained release (up to 24 h) of ginsenoside Rb1 (GRb1) is revealed by the dissolution study of PM. A significantly (p < 0.05) greater anti-oxidant (AO) potential of PM can well be perceived as of the diminution in the lipid peroxidase level in addition to the rise in the glutathione superoxide dismutase (SOD) in addition to catalase levels. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold together with the diminution in damage to nerves. A noteworthy enhancement in the relative BA (157.94%) of GRb1 through the PM formulation can well be seen in the PK studies. Conclusion: It is exhibited that the PM system is an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathic pain.

Keywords: ginseng, neuropathic, phytosome, pain

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Authors: Tamer M. Shehata, Heba S. Elsewedy, Mashel Al Dosary, Alaa Elshehry, Mohamed A. Khedr, Maged E. Mohamed

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Objective: 2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known herbicide widely used as a weed killer. Recently, 2,4-D was rediscovered as a new anti-inflammatory agent through in silico as well as in-vivo experiments. However, poor solubility of 2,4-D could represent a problems during pharmaceutical development in addition to lower bioavailability. Solid dispersion (SD) refers to a group of solid products consisting of at least two different components, usually a hydrophobic drug and hydrophilic matrix. It is well known technique for enhancing drug solubility. Therefore, selecting SD as a tool for enhancing 2,4-D could be of great interest to the formulator. Method: In our project, several polymers were investigated (such as PEG, HPMC, citric acid and others) in addition to drug polymer ratios and its effect on solubility. Evaluation of drug polymer interaction was investigated through both Fourier Transform Infrared (FTIR) and Differential Scanning Calorimetry (DSC). Finally, in-vivo evaluation was performed for the best selected preparation through inflammatory response of rat induce hind paw. Results: Results indicated that, citric acid 2,4-D and in ratio of 0.75 : 1 showed modified the dissolution profile of the drug. The FTIR resltes indicated no significant chemical interaction, however DSC showed shifting of the drug melting point. Finally, Carragenan induced rat hind paw edema showed significant reduction of the drug solid dispersion in comparison to the pure drug, indicating rapid and complete absorption of the drug in solid dispersion form. Conclusion: Solid dispersion technology can be utilized efficiently to enhance the solubility of 2,4-D.

Keywords: solid dispersion, 2, 4-D solubility, carragenan induced edema

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Authors: Ana-Maria Gheldiu, Bianca M. Abrudan, Maria A. Neag, Laurian Vlase, Dana M. Muntean

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Background information: The objective of this study was to investigate the effect of multiple-dose fluvoxamine on the pharmacokinetic profile of single-dose carvedilol in rats, in order to evaluate this possible drug-drug pharmacokinetic interaction. Methods: A preclinical study, in 28 white male Wistar rats, was conducted. Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) in the absence of fluvoxamine or after a pre-treatment with multiple oral doses of fluvoxamine (14.28 mg/kg b.m.). The plasma concentrations of carvedilol were estimated by high performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters of carvedilol were analyzed by non-compartmental method. Results: After carvediol co-administration with fluvoxamine, an approximately 2-fold increase in the exposure of carvedilol was observed, considering the significantly elevated value of the total area under the concentration versus time curve (AUC₀₋∞). Moreover, an increase by approximately 145% of the peak plasma concentration was found, as well as an augmentation by approximately 230% of the half life time of carvedilol was observed. Conclusion: Fluvoxamine co-administration led to a significant alteration of carvedilol’s pharmacokinetic profile in rats, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition. Acknowledgement: This work was supported by CNCS Romania – project PNII-RU-TE-2014-4-0242.

Keywords: carvedilol, fluvoxamine, drug-drug pharmacokinetic interaction, rats

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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

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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

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Authors: Ozlem Karabulutlu, Kiymet Yesilcicek Calik, Nazli Akar

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Objectives: To examine fear of childbirth according to parity, gestational age, prenatal education, and obstetric history. Methods: The study was performed as a questionnaire design in a State Hospital in Kars, Turkey with 403 unselected pregnant who were recruited from the delivery unit. The data were collected via 3 questionnaires; the first with sociodemographic and obstetric features, the second with Wijma Delivery Expectance/Experience Questionnaire (W-DEQ) scale, and the third with the scale of Beck Anxiety Inventory (BAI). Results: The W-DEQ and BAI scores were higher in nulliparous than multiparous woman (W-DEQ 67.08±28.33, 59.87±26.91, P=0.039<0.05, BAI 18.97±9.5, 16.65±11.83, P=0.0009<0.05 respectively). Moreover, W-DEQ and BAI scores of pregnant whose gestational week was ≤37 / ≥41 and who didn’t receive training and had vaginal delivery was higher than those whose gestational week was 38-40 weeks and who received prenatal training and had cesarean delivery (W-DEQ 67.54±29.20, 56.44±22.59, 69.72±25.53 p<0.05, BAI 21.41±9.07; 15.77±11.20, 18.36±10.57 p<0.05 respectively). Both in nulliparous and multiparous, as W-DEQ score increases BAI score increases too (r=0.256; p=0.000<0.05). Conclusions: Severe fear of childbirth and anxiety was more common in nulliparous women, preterm and post-term pregnancy and who did not receive prenatal training and had vaginal delivery.

Keywords: Beck Anxiety Inventory (BAI), fear of birth, parity, pregnant women, Wijma Delivery Expectance/Experience Questionnaire (W-DEQ)

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Authors: Mandisi Matyana

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Although the South African local government is doing all the best in ensuring improved service delivery for the citizens, service delivery disparity still remains the real challenge for other municipalities. The unequal distribution of services within municipal wards is causing unequal happiness among the citizens; hence others do enjoy different provided municipal services, while others do not. It is acknowledged that less access to municipal services infringes one’s rights, such as the right to human dignity and the right to life. Some of the municipal services are basic services and they are the mainstay of human survival, such as water, housing, etc. It is quite evident that the service delivery disparity could be caused by the various factors within the local municipality affairs, including both administrative and political factors. Therefore, this study is undertaken to check and evaluate the main foundations of service delivery disparity in ensuring equal development of the state, particularly for local communities. The study used the qualitative method to collect the data from the citizens of Winnie Madikizela Mandela Local Municipality. An extensive literature was also conducted in understanding the causes of service delivery disparity. Study findings prove that the service delivery disparity could be caused by factors such as political interference in administration, corruption and fraud, elevated unemployment levels, inadequate institutional capacity, etc. Therefore, the study recommends strong community participation and constant external supervision in the local government so as to encourage openness in local government to ensure fair administration towards services to be provided.

Keywords: administration, development, municipal services, service delivery disparity, Winnie Madikizela Mandela local municipality

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Authors: Lilian A. Okeke, I. Okeke, N. Waziri, S. Balogun, P. Nguku, O. Fawole

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Background: Access to ante-natal care services promotes safe motherhood and delivery with improved maternal and neonatal outcome. We conducted this study to identify factors influencing the utilization of antenatal care (ANC) and health delivery services. Methods: We conducted a cross sectional study. Households were numbered and a one in three sample was selected using a systematic sampling method. One hundred and ninety eight women who were either pregnant or had previous deliveries were interviewed using pretested structured questionnaires to obtain information on their socio-demographic characteristics, and reasons for non-utilization of ANC and health delivery services. We performed univariate and bivariate analysis using Epi info version 3.5.3. Results: The age of respondents ranged from (17-55 years) with a median age of 29 years. One hundred and ninety two (97%) utilized antenatal care services. Ninety three (47.9%) attended ANC at second trimester. More than half (58.6%) had ≥ 4 visits to ANC. One hundred and thirty one (66.2%) had their last delivery at home by a traditional birth attendant. Factors associated with ANC and health facility delivery services utilization were: age group 45-55 (OR 0.01; 95% CI: 0.00-0.16) and > 55 years (OR 0.03; 95% CI: 0.00-0.60), wife’s educational status (OR 3.17; 95% CI: 1.66-8.30), husband’s permission (OR 11.8; 95% CI 2.19-63.62), and distance ≥ 5km (OR 0.33; 95% CI: 0.16-0.60). Conclusion: ANC services were well utilized. Most women did not book early and had their last delivery at home. Predictors of ANC use and health facility delivery were age, wife’s educational status, husband's permission and long distance from health facility. A one-day health sensitization of the benefits of ANC utilization and the dangers of delivering at home was implemented.

Keywords: ante natal care, health facility, delivery services, rural area, Plateau state

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Authors: Fernando G. Torres, Omar P. Troncoso

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Starch is a highly biocompatible, non-toxic, and biodegradable polymer. It is widely used in biomedical applications, including drug delivery systems and tissue engineering scaffolds. Curcumin, a phenolic compound found in the dried root of Curcuma longa, has been used as a nutritional supplement due to its antimicrobial, anti-inflammatory, and antioxidant effects. However, the major problem with ingesting curcumin by itself is its poor bioavailability due to its poor absorption and rapid metabolism. In this study, we report a novel methodology to prepare starch nanoparticles loaded with curcumin. The nanoparticles were synthesized via nanoprecipitation of starch granules extracted from native Andean potatoes (Solanum tuberosum ssp. and Andigena var Huamantanga varieties). The nanoparticles were crosslinked and stabilized by using sodium tripolyphosphate and Tween®80, respectively. The characterization of the nanoparticles loaded with curcumin was assessed by Fourier Transform Infrared Spectroscopy, Dynamic Light Scattering, Zeta potential, and Differential scanning calorimetry. UV-vis spectrophotometry was used to evaluate the loading efficiency and capacity of the samples. The results showed that native starch nanoparticles could be used to prepare promising nanocarriers for the controlled release of curcumin.

Keywords: starch nanoparticle, nanoprecipitation, curcumin, biomedical applications

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Authors: Saeedeh Ahmadi Basir, Mohammad Mahdavi Mazdeh, Mohammad Namakshenas

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Manufacturers often dispatch jobs in batches to reduce delivery costs. However, sending several jobs in batches can have a negative effect on other scheduling-related objective functions such as minimizing the number of tardy jobs which is often used to rate managers’ performance in many manufacturing environments. This paper aims to minimize the number of weighted tardy jobs and the sum of delivery costs of a two-stage assembly flow-shop problem in a batch delivery system. We present a mixed-integer linear programming (MILP) model to solve the problem. As this is an MILP model, the commercial solver (the CPLEX solver) is not guaranteed to find the optimal solution for large-size problems at a reasonable amount of time. We present several numerical examples to confirm the accuracy of the model.

Keywords: scheduling, two-stage assembly flow-shop, tardy jobs, batched delivery system

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Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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Authors: Rui Chen, Jinfeng Zhang, Chun-Sing Lee

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In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive biodegradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy.

Keywords: carbon nitride, combination therapy, drug delivery, nanoscale metal-organic frameworks

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Authors: Azwin Lubis, Rika Hapsari, Zahrah Hikmah, Anang Endaryanto, Ariyanto Harsono

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Erythema Multiforme Exudativum Major (EMEM) is one of the drug allergy diseases. Drug allergies caused by isoniazid rarely causes EMEM. Cutaneous reactions caused by isoniazid were obtained in 0.98% of patients, but the precise occurrence of Steven Johnson’s Syndrome (SJS) and Toxic Epidermolisis Necrolisis (TEN) due to isoniazid is not known for certain. We present this case to show hypersensitivity of isoniazid in a child. Based on the history of drug intake, physical diagnostic tests, drug elimination and provocation; we established the diagnosis of isoniazid hypersensitivity. The child showed improvement on skin manifestation after stopped isoniazid therapy.

Keywords: erythema multiforme exudativum major, hypersensitivity, elimination test, provocation test

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Authors: Nipun Agarwal, David Paul, Fareed Un Din

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Every organization develops a strategy that needs to be implemented and is undertaken through project delivery. In essence, project requirements should exactly replicate an organization’s strategy. In reality this does not happen, and behavioral factors deviate the project delivery from the strategic objectives. This occurs as project stakeholders can have competing objectives. Resultantly, requirements that are implemented through projects are less aligned to the strategy. This paper develops a game theoretic model to simulate why such deviations occur. That explains the difference between strategy development and implementation.

Keywords: strategy, simulation, project management, game theory

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Authors: Shilpa Bhilegaonkar, Ram Gaud

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Candesartan cilexetil is a poorly soluble antihypertensive agent with solubility limited bioavailability (15%). To initiate process of solubilisation, it is very much necessary to displace the air at the surface and wet the drug surface with a solvent, with which drug is compatible. Present research adopts the same principle to improve solubility and dissolution of candesartan cilexetil. Solvents used here are surfactant and modified surfactant in different drug: solvent (1:1-1:9) ratio’s for preparation of adsorbates. Adsorbates were then converted into free flowing powders as liquisolid compacts and compressed to form tablets. Liquisolid compacts were evaluated for improvement in saturation solubility and dissolution of candesartan cilexetil. All systems were evaluated for improvement in saturation solubility and dissolution in different medias such as water, 0.1 N HCl, Phosphate buffer pH 6.8 and media given by office of generic drugs along with other physicochemical testing. All systems exhibited a promising advantage in terms of solubility and dissolution without affecting the drug structure as confirmed by IR and XRD. No considerable advantage was seen of increasing solvent ratio with drug.

Keywords: candesartan cilexetil, improved dissolution, solubility, liquisolid

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Authors: Ghaleb A. Husseini, Salma E. Ahmed, Hesham G. Moussa, Ana M. Martins, Mohammad Al-Sayah, Nasser Qaddoumi

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This abstract aims to investigate the use of targeted liposomes as anticancer drug carriers in vitro in combination with ultrasound applied as drug trigger; in order to reduce the side effects caused by traditional chemotherapy. Pegylated liposomes were used to encapsulate calcein and then release this model drug when 20-kHz, 40-kHz, 1-MHz and 3-MHz ultrasound were applied at different acoustic power densities. Fluorescence techniques were then used to measure the percent drug release of calcein from these targeted liposomes. Results showed that as the power density increases, at the four frequencies studied, the release of calcein also increased. Based on these results, we believe that ultrasound can be used to increase the rate and amount of chemotherapeutics release from liposomes.

Keywords: liposomes, calcein release, high frequency ultrasound, low frequency ultrasound, fluorescence techniques

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Authors: Abhay Asthana, Shally Toshkhani, Gyati Shilakari

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The objective of the present research work is to develop a topical biodegradable dermal patch based formulation to aid accelerated wound healing. It is always better for patient compliance to be able to reduce the frequency of dressings with improved drug delivery and overall therapeutic efficacy. In present study optimized formulation using biodegradable components was obtained evaluating polymers and excipients (HPMC K4M, Ethylcellulose, Povidone, Polyethylene glycol and Gelatin) to impart significant folding endurance, elasticity, and strength. Molten gelatin was used to get a mixture using ethylene glycol. Chitosan dissolved in acidic medium was mixed with stirring to Gelatin mixture. With continued stirring to the mixture Curcumin was added with the aid of DCM and Methanol in an optimized ratio of 60:40 to get homogenous dispersion. Polymers were dispersed with stirring in the final formulation. The mixture was sonicated casted to get the film form. All steps were carried out under strict aseptic conditions. The final formulation was a thin uniformly smooth textured film with dark brown-yellow color. The film was found to have folding endurance was around 20 to 21 times without a crack in an optimized formulation at RT (23°C). The drug content was in range 96 to 102% and it passed the content uniform test. The final moisture content of the optimized formulation film was NMT 9.0%. The films passed stability study conducted at refrigerated conditions (4±0.2°C) and at room temperature (23 ± 2°C) for 30 days. Further, the drug content and texture remained undisturbed with stability study conducted at RT 23±2°C for 45 and 90 days. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as tested in vivo with correlation factor R2>0.9. In in vivo study administration of one dose in equivalent quantity per 2 days was applied topically. The data demonstrated a significant improvement with percentage wound contraction in contrast to control and plain drug respectively in given period. The film based formulation developed shows promising results in terms of stability and in vivo performance.

Keywords: wound healing, biodegradable, polymers, patch

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Authors: Vergeena Varghese, G. Gajalakshmi, Jayarajini Vasanth

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The present study deals with the indication of prevalence of dry eye and evaluates environmental risk factors attributed to dry eye in different occupational sectors. 240 subjects above 20 years and below 45 years of age were screened for dry eye. Mcmonnies dry eye questionnaire based history and Schirmer’s test were used to diagnose dry eye. For Schirmer’s test Whatman strip and paracaine drop used as an anesthetic. Subject’s demographics include age, sex, smoking, alcoholism, occupation history and working environment. Out of a total of 240 subjects, 52 subjects were positive for dry eye syndrome (21.7%). The highest prevalence of dry eye syndrome in software sector was 14subjects (26.9%) out of a total of 40 subjects. In the construction sector, the prevalence of dry eye syndrome had 12 subjects (23.1%) out of 40 subjects and 9 subjects (17.3%) out of 40 subjects in agriculture sector. 7 subjects (13.5%) who had dry eye out of 40 subjects in the transport sector and in industrial 6 subjects (11.5%). In a normal sector, this was taken as control group had dry eye in 4 subjects (7.7%) out of 40 subjects. We also found the prevalence of dry eye in OS was higher than OD. Dry eye is a most common ocular condition. The highest prevalence of dry eye syndrome in software sector was 14 members than other sector. There was a significant correlation between environmental and occupational factors to cause dry eye. Excessive exposure to sunlight, wind, high temperature, and air pollution, electromagnetic radiation are the factors affect the tear film and ocular surface causing the dry eye syndrome.

Keywords: DES – dry eye syndrome, Mcmonnies dry eye questionnaire, schirmer’s test, whatman vstrip

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Authors: Smruti Mahapatra, Dipankar Biswas, Richard Um, Michael Meggyesy, Riccardo Serra, Noah Gorelick, Steven Marra, Amir Manbachi, Mark G. Luciano

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Intracranial pressure (ICP) is profoundly regulated by the effects of cardiac pulsation and the volume of the incoming blood. Furthermore, these effects on ICP are incremented by the presence of a rigid skull that does not allow for changes in total volume during the cardiac cycle. These factors play a pivotal role in cerebrospinal fluid (CSF) dynamics and distribution, with consequences that are not well understood to this date and that may have a deep effect on the Central Nervous System (CNS) functioning. We designed this study with two specific aims: (a) To study how pulsatility influences local CSF flow, and (b) To study how modulating intracranial pressure affects drug distribution throughout the SAS globally. In order to achieve these aims, we built an elaborate in-vitro model of the SAS closely mimicking the dimensions and flow rates of physiological systems. To modulate intracranial pressure, we used an intracranially implanted, cardiac-gated, volume-oscillating balloon (CADENCE device). Commercially available dye was used to visualize changes in CSF flow. We first implemented two control cases, seeing how the tracer behaves in the presence of pulsations from the brain phantom and the balloon individually. After establishing the controls, we tested 2 cases, having the brain and the balloon pulsate together in sync and out of sync. We then analyzed the distribution area using image processing software. The in-sync case produced a significant increase, 5x times, in the tracer distribution area relative to the out-of-sync case. Assuming that the tracer fluid would mimic blood flow movement, a drug introduced in the SAS with such a system in place would enhance drug distribution and increase the bioavailability of therapeutic drugs to a wider spectrum of brain tissue.

Keywords: blood-brain barrier, cardiac-gated, cerebrospinal fluid, drug delivery, neurosurgery

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Authors: Somdutt Mujwar, Kamal Raj Pardasani

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Cholera pandemics are caused by facultative pathogenic Vibrio cholera bacteria persisting in the countries having warmer climatic conditions as well as the presence of large water bodies with huge amount of organic matter, it is responsible for the millions of deaths annually. Presently the available therapy for cholera is Oral Rehydration Therapy (ORT) with an antibiotic drug. Excessive utilization of life saving antibiotics drugs leads to the development of resistance by the infectious micro-organism against the antibiotic drugs resulting in loss of effectiveness of these drugs. Also, many side effects are also associated with the use of these antibiotic drugs. This riboswitch is explored as an alternative drug target for Vibrio cholera bacteria to overcome the problem of drug resistance as well as side effects associated with the antibiotics drugs. The bacterial riboswitch is virtually screened with 24407 legends to get possible drug candidates. The 10 ligands showing best binding with the riboswitch are selected to design a pharmacophore, which can be utilized to design lead molecules by using the phenomenon of bioisosterism.

Keywords: cholera, drug design, ligand, riboswitch, pharmacophore

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Authors: Mohammad Karam, Abdulmalik Alsaif, Abdulrahman Al-Naseem, Amrit Hayre, Abdurrahman Al Jabbouri, Ahmad Aldubaikhi, Narvair Kahlar, Salem Al-Mutairi

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Purpose: To compare the outcomes of mycophenolate mofetil (MMF) versus methotrexate (MTX) in non-infectious ocular inflammatory disease (NIOID). Methods: A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines and an electronic search was conducted to identify all comparative studies of MMF versus MTX in NIOID. Treatment results and side effects were primary outcome measures. Secondary outcome measures included visual acuity and resolution of macular oedema. Fixed and random-effects models were used for the analysis. Results: Four studies enrolling 905 patients were identified. There was no significant difference between MMF and MTX groups in overall treatment success (Odds Ratio [OR] = 0.97, P = 0.96) and failure (OR = 0.86, P = 0.85) of NIOID. Although treatment success of uveitis showed no significant difference for anterior and intermediate uveitis cases (OR = 2.33, P = 0.14), MTX showed a significantly improved effect in cases involving posterior uveitis and panuveitis (OR = 0.41, P = 0.003). However, the median dose required for treatment success was lower for MTX whereas MMF was associated with a faster median time to treatment success. Further to this, MMF showed a reduced rate of side effects when compared to MTX, but MTX failed to reach statistical significance, most notably for liver enzyme elevation (OR = 0.65, P = 0.16), fatigue (OR = 0.84, P = 0.49) and headache (OR = 0.81, P = 0.37). For secondary outcomes, no significant difference was noted in visual acuity and resolution of macular edema. Conclusions: MMF is comparable to MTX in the treatment of NIOID as there was no significant difference in the outcome of treatment success and side effect profiles.

Keywords: Mycophenolate mofetil, methotrexate, non-infectious ocular inflammation, uveitis, scleritis

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Authors: Mauro Masili, Liliane Ventura

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It is still controversial in the literature the ultraviolet (UV) radiation effects on the ocular media, but the World Health Organization has established safe limits on the exposure of eyes to UV radiation based on reports in literature. Sunglasses play an important role in providing safety, and their lenses should provide adequate UV filters. Regarding UV protection for ocular media, the resistance-to-irradiance test for sunglasses under many national standards requires irradiating lenses for 50 uninterrupted hours with a 450 W solar simulator. This artificial aging test may provide a corresponding evaluation of exposure to the sun. Calculating the direct and diffuse solar irradiance at a vertical surface and the corresponding radiant exposure for the entire year, we compare the latter with the 50-hour radiant exposure of a 450 W xenon arc lamp from a solar simulator required by national standards. Our calculations indicate that this stress test is ineffective in its present form. We provide evidence of the need to re-evaluate the parameters of the tests to establish appropriate safe limits against UV radiation. This work is potentially significant for scientists and legislators in the field of sunglasses standards to improve the requirements of sunglasses quality and safety.

Keywords: ISO 12312-1, solar simulator, sunglasses standards, UV protection

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Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

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Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

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Authors: Minh Thi Hai Vo

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This article draws on in-depth interviews with state employees at public hospitals and universities in its institutional analysis of the autonomy practices of public service delivery units in Vietnam. Unlike many empirical and theoretical studies that view formal and informal institutions as complements or substitutes, this article finds no evidence of complementary or substitutive relationships. Instead, the article finds that formal institutions accommodate informal ones and that informal institutions tend to compete and interfere, with the existing and ineffective formal institutions. The result of such conflicting relationship is that the actual autonomy of public service delivery units is, in most cases, perceived to be greater than the formal autonomy they are given. In the condition of poor regulation, the informal autonomy may result in unethical practices including rent-seeking and corruption. The implication of the study finding is policy-makers need to redesign and reorganize the autonomisation of public service delivery units to make informal institutions support and reinforce formal ones in a complementary manner.

Keywords: autonomy, formal institutions, informal institutions, public service delivery units, Vietnam

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Authors: Vano Tsertsvadze, Marina Chavchanidze, Lali Khurtsia

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Problem of drug use is often seen as a combination of psychological and social problems, but this problem can be considered as economically rational decision in the process of buying pleasure (looking after children, reading, harvesting fruits in the fall, sex, eating, etc.). Before the adoption of the decisions people face to a trade-off - when someone chooses a delicious meal, she takes a completely rational decision, that the pleasure of eating has a lot more value than the pleasure which she will experience after two months diet on the summer beach showing off her beautiful body. This argument is also true for alcohol, drugs and cigarettes. Smoking has a negative effect on health, but smokers are not afraid of the threat of a lung cancer after 40 years, more valuable moment is a pleasure from smoking. Our hypothesis - unsatisfied pleasure and frustration, probably determines the risk of dependence on drug abuse. The purpose of research: 1- to determine the relative measure unit of pleasure, which will be used to measure and assess the intensity of various human pleasures. 2- to compare the intensity of the pleasure from different kinds of activity, with pleasures received from drug use. 3- Based on the analysis of data, to identify factors affecting the rational decision making. Research method: Respondents will be asked to recall the greatest pleasure of their life, which will be used as a measure of the other pleasures. The study will use focus groups and structured interviews.

Keywords: drug, drug-user, measurement, satisfaction

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