Search results for: drug retail outlets
1952 Green Synthesis (Using Environment Friendly Bacteria) of Silver-Nanoparticles and Their Application as Drug Delivery Agents
Authors: Sutapa Mondal Roy, Suban K. Sahoo
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The primary aim of this work is to synthesis silver nanoparticles (AgNPs) through environmentally benign routes to avoid any chemical toxicity related undesired side effects. The nanoparticles were stabilized with drug ciprofloxacin (Cp) and were studied for their effectiveness as drug delivery agent. Targeted drug delivery improves the therapeutic potential of drugs at the diseased site as well as lowers the overall dose and undesired side effects. The small size of nanoparticles greatly facilitates the transport of active agents (drugs) across biological membranes and allows them to pass through the smallest capillaries in the body that are 5-6 μm in diameter, and can minimize possible undesired side effects. AgNPs are non-toxic, inert, stable, and has a high binding capacity and thus can be considered as biomaterials. AgNPs were synthesized from the nutrient broth supernatant after the culture of environment-friendly bacteria Bacillus subtilis. The AgNPs were found to show the surface plasmon resonance (SPR) band at 425 nm. The Cp capped Ag nanoparticles formation was complete within 30 minutes, which was confirmed from absorbance spectroscopy. Physico-chemical nature of the AgNPs-Cp system was confirmed by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) etc. The AgNPs-Cp system size was found to be in the range of 30-40 nm. To monitor the kinetics of drug release from the surface of nanoparticles, the release of Cp was carried out by careful dialysis keeping AgNPs-Cp system inside the dialysis bag at pH 7.4 over time. The drug release was almost complete after 30 hrs. During the drug delivery process, to understand the AgNPs-Cp system in a better way, the sincere theoretical investigation is been performed employing Density Functional Theory. Electronic charge transfer, electron density, binding energy as well as thermodynamic properties like enthalpy, entropy, Gibbs free energy etc. has been predicted. The electronic and thermodynamic properties, governed by the AgNPs-Cp interactions, indicate that the formation of AgNPs-Cp system is exothermic i.e. thermodynamically favorable process. The binding energy and charge transfer analysis implies the optimum stability of the AgNPs-Cp system. Thus, the synthesized Cp-Ag nanoparticles can be effectively used for biological purposes due to its environmentally benign routes of synthesis procedures, which is clean, biocompatible, non-toxic, safe, cost-effective, sustainable and eco-friendly. The Cp-AgNPs as biomaterials can be successfully used for drug delivery procedures due to slow release of drug from nanoparticles over a considerable period of time. The kinetics of the drug release show that this drug-nanoparticle assembly can be effectively used as potential tools for therapeutic applications. The ease of synthetic procedure, lack of possible chemical toxicity and their biological activity along with excellent application as drug delivery agent will open up vista of using nanoparticles as effective and successful drug delivery agent to be used in modern days.Keywords: silver nanoparticles, ciprofloxacin, density functional theory, drug delivery
Procedia PDF Downloads 3581951 Preparation and Characterization of Poly (ε-caprolactone) Loaded with Layered Double Hydroxide Nanohybrid Intercalated with Alendronate for Osteoporosis Treatment
Authors: Seyedeh Faranak Baniahmad, Soroor Yousefi
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Osteoporosis is a bone disease which increases the bone fracture risk, reduces the bone mineral density (BMD) and alters the amount and variety of proteins in bones. Antiresorptive therapy is one the most popular Osteoporosis treatment methods. In this method the bisphosphonates, hormones, calcitonin or the selective estrogen receptor modulators is replaced. In order to reduce undesirable effects and to increase the bioavailability of drug agents, the controlled drug delivery systems have been utilized. In current study, the controlled release of Alendronate from LDH-PCL with (0, 5, 10, 15 % wt. of LDH) was investigated. The results showed that the release of alendronate from the lamellar LDH incorporated into the PCL matrix is much slower than the release of alendronate from the PCL. Therefore such systems are very promising, in which the antiresorptive drug has to remain in the matrix for longer time and can be released in controlled manner.Keywords: osteoporosis, alendronate, poly (ε–caprolactone), layered double hydroxide
Procedia PDF Downloads 3561950 Sexual Behaviors and Condom Attitude among Injecting Drug Users in Hai Phong, Vietnam: Qualitative Findings
Authors: Tanvir Ahmed, Thanh N. Long, Phan T. Huong, Donald E. Stewart
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This paper presents views on condom use and the contexts of safe and unsafe sexual practices with different sexual partners and their relationships among Injecting Drug Users (IDUs) in Hai Phong, Vietnam. Fifteen IDUs participated and two local interviewers conducted qualitative semi-structured face-to-face interviews in September-October, 2012 in Vietnamese language. Data were analyzed thematically. Non-protective condom attitudes include negotiate or convince Female Sex Workers (FSW); not realizing risk, importance or necessity; partner doesn’t like, and having extra money/drug from clients. On the other hand, self-awareness, family-consciousness, suspicion of STI presence, fear of getting HIV, and client negotiation sometimes resulted in a safe-sex practice. A thematic diagram was developed to present the relationship (strong/weak) between condom attitude and sexual practice (safe/unsafe) by partner types. The experiences and views reflected in the qualitative information emphasize the heightened need for safe-sex education especially among young IDUs (male/female) highlighting sexual transmission risk.Keywords: AIDS, HIV, injecting drug user, risk behaviors, Vietnam
Procedia PDF Downloads 8321949 Isolation and Characterization of Anti-melanoma (Skin Cancer) Compounds from Corchorus olitorius .L
Authors: Peramachi Sathiyamoorthy, Jacop Gopas, Avi Golan Goldhirsh
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Corchorus olitorius is a leafy vegetable and an industrial crop. The herb has antioxidant, anti inflammatory, and anti-cancer properties. To assay the pharmaceutical properties, aqueous extracts of leaves and seeds from C. olitorius were tested against drug resistant melanoma cell line. The test showed LC50 of the extract was 0.08µg/ml. Aqueous seed extract exhibited higher melanoma inhibiting activity than leaf extract. Dialysis of seed extract showed that the active compound is less than 12 KDa. The compound with <3 KDa MW separated by microconcentration of seed extract showed 70.5 % inhibition of melanoma cell growth. Among the two fractions obtained by Gel filtration with G10 column, the first fraction at 1:2000 dilutions exhibited 100% inhibition of melanoma growth. The compound with Rf value 0.86 (MA4) isolated by TLC separation showed about 98% cytotoxicity against melanoma at 1: 1000 dilutions. Furthermore, HPLC separation of MA4 compound with Superdex 75 column resulted in 4 compounds. Out of 4, one compound showed melanoma inhibition. The active compound is identified by reagent methods as Strophanthidin. Further toxicological and clinical studies will lead to the development of a potential drug to treat drug resistant melanoma.Keywords: corchorus olitorius, melanoma, drug development, strophanthidin
Procedia PDF Downloads 1051948 Synthesis of a Hybrid of PEG-b-PCL and G1-PEA Dendrimer Based Six-Armed Star Polymer for Nano Delivery of Vancomycin
Authors: Calvin A. Omolo, Rahul S. Kalhapure, Mahantesh Jadhav, Sanjeev Rambharose, Chunderika Mocktar, Thirumala Govender
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Treatment of infections is compromised by limitations of conventional dosage forms and drug resistance. Nanocarrier system is a strategy to overcome these challenges and improve therapy. Thus, the development of novel materials for drug delivery via nanocarriers is essential. The aim of the study was to synthesize a multi-arm polymer (6-mPEPEA) for enhanced activity of vancomycin (VM) against susceptible and resistant Staphylococcus aureus (MRSA). The synthesis steps of the star polymer followed reported procedures. The synthesized 6-mPEPEA was characterized by FTIR, ¹H and ¹³CNMR and MTT assays. VM loaded micelles were prepared from 6-mPEPEA and characterized for size, polydispersity index (PI) and surface charge (ZP) (Dynamic Light Scattering), morphology by TEM, drug loading (UV Spectrophotometry), drug release (dialysis bag), in vitro and in vivo efficacy against sensitive and resistant S. aureus. 6-mPEPEA was synthesized, and its structure was confirmed. MTT assays confirmed its nontoxic nature with a high cell viability (77%-85%). Unimolecular spherical micelles were prepared. Size, PI, and ZP was 52.48 ± 2.6 nm, 0.103 ± 0.047, -7.3 ± 1.3 mV, respectively and drug loading was 62.24 ± 3.8%. There was a 91% drug release from VCM-6-mPEPEA after 72 hours. In vitro antibacterial test revealed that VM-6-mPEPEA had 8 and 16-fold greater activity against S. aureus and MRSA when compared to bare VM. Further investigations using flow cytometry showed that VM-6-mPEPEA had 99.5% killing rate of MRSA at the MIC concentration. In vivo antibacterial activity revealed that treatment with VM-6-mPEPEA had a 190 and a 15-fold reduction in the MRSA load in untreated and VM treated respectively. These findings confirmed the potential of 6-mPEPEA as a promising bio-degradable nanocarrier for antibiotic delivery to improve treatment of bacterial infections.Keywords: biosafe, MRSA, nanocarrier, resistance, unimolecular-micelles
Procedia PDF Downloads 1571947 Exploring Twitter Data on Human Rights Activism on Olympics Stage through Social Network Analysis and Mining
Authors: Teklu Urgessa, Joong Seek Lee
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Social media is becoming the primary choice of activists to make their voices heard. This fact is coupled by two main reasons. The first reason is the emergence web 2.0, which gave the users opportunity to become content creators than passive recipients. Secondly the control of the mainstream mass media outlets by the governments and individuals with their political and economic interests. This paper aimed at exploring twitter data of network actors talking about the marathon silver medalists on Rio2016, who showed solidarity with the Oromo protesters in Ethiopia on the marathon race finish line when he won silver. The aim is to discover important insight using social network analysis and mining. The hashtag #FeyisaLelisa was used for Twitter network search. The actors’ network was visualized and analyzed. It showed the central influencers during first 10 days in August, were international media outlets while it was changed to individual activist in September. The degree distribution of the network is scale free where the frequency of degrees decay by power low. Text mining was also used to arrive at meaningful themes from tweet corpus about the event selected for analysis. The semantic network indicated important clusters of concepts (15) that provided different insight regarding the why, who, where, how of the situation related to the event. The sentiments of the words in the tweets were also analyzed and indicated that 95% of the opinions in the tweets were either positive or neutral. Overall, the finding showed that Olympic stage protest of the marathoner brought the issue of Oromo protest to the global stage. The new research framework is proposed based for event-based social network analysis and mining based on the practical procedures followed in this research for event-based social media sense making.Keywords: human rights, Olympics, social media, network analysis, social network ming
Procedia PDF Downloads 2211946 Development of Nanostructrued Hydrogel for Spatial and Temporal Controlled Release of Active Compounds
Authors: Shaker Alsharif, Xavier Banquy
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Controlled drug delivery technology represents one of the most rapidly advancing areas of science in which chemists and chemical engineers are contributing to human health care. Such delivery systems provide numerous advantages compared to conventional dosage forms including improved efficacy, and improved patient compliance and convenience. Such systems often use synthetic polymers as carriers for the drugs. As a result, treatments that would not otherwise be possible are now in conventional use. The role of bilayered vesicles as efficient carriers for drugs, vaccines, diagnostic agents and other bioactive agents have led to a rapid advancement in the liposomal drug delivery system. Moreover, the site avoidance and site-specific drug targeting therapy could be achieved by formulating a liposomal product, so as to reduce the cytotoxicity of many potent therapeutic agents. Our project focuses on developing and building hydrogel with nanoinclusion of liposomes loaded with active compounds such as proteins and growth factors able to release them in a controlled fashion. In order to achieve that, we synthesize several liposomes of two different phospholipids concentrations encapsulating model drug. Then, formulating hydrogel with specific mechanical properties embedding the liposomes to manage the release of active compound.Keywords: controlled release, hydrogel, liposomes, active compounds
Procedia PDF Downloads 4221945 Combined Effect of Vesicular System and Iontophoresis on Skin Permeation Enhancement of an Analgesic Drug
Authors: Jigar N. Shah, Hiral J. Shah, Praful D. Bharadia
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The major challenge faced by formulation scientists in transdermal drug delivery system is to overcome the inherent barriers related to skin permeation. The stratum corneum layer of the skin is working as the rate limiting step in transdermal transport and reduce drug permeation through skin. Many approaches have been used to enhance the penetration of drugs through this layer of the skin. The purpose of this study is to investigate the development and evaluation of a combined approach of drug carriers and iontophoresis as a vehicle to improve skin permeation of an analgesic drug. Iontophoresis is a non-invasive technique for transporting charged molecules into and through tissues by a mild electric field. It has been shown to effectively deliver a variety of drugs across the skin to the underlying tissue. In addition to the enhanced continuous transport, iontophoresis allows dose titration by adjusting the electric field, which makes personalized dosing feasible. Drug carrier could modify the physicochemical properties of the encapsulated molecule and offer a means to facilitate the percutaneous delivery of difficult-to-uptake substances. Recently, there are some reports about using liposomes, microemulsions and polymeric nanoparticles as vehicles for iontophoretic drug delivery. Niosomes, the nonionic surfactant-based vesicles that are essentially similar in properties to liposomes have been proposed as an alternative to liposomes. Niosomes are more stable and free from other shortcoming of liposomes. Recently, the transdermal delivery of certain drugs using niosomes has been envisaged and niosomes have proved to be superior transdermal nanocarriers. Proniosomes overcome some of the physical stability related problems of niosomes. The proniosomal structure was liquid crystalline-compact niosomes hybrid which could be converted into niosomes upon hydration. The combined use of drug carriers and iontophoresis could offer many additional benefits. The system was evaluated for Encapsulation Efficiency, vesicle size, zeta potential, Transmission Electron Microscopy (TEM), DSC, in-vitro release, ex-vivo permeation across skin and rate of hydration. The use of proniosomal gel as a vehicle for the transdermal iontophoretic delivery was evaluated in-vitro. The characteristics of the applied electric current, such as density, type, frequency, and on/off interval ratio were observed. The study confirms the synergistic effect of proniosomes and iontophoresis in improving the transdermal permeation profile of selected analgesic drug. It is concluded that proniosomal gel can be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions.Keywords: iontophoresis, niosomes, permeation enhancement, transdermal delivery
Procedia PDF Downloads 3541944 Improving the Employee Transfer Experience within an Organization
Authors: Drew Fockler
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This research examines how to improve an employee’s experience when transferring between departments within an organization. This research includes a historical review of a Canadian retail organization. Based on this historical review, gaps are identified between current and future visions to show where problems with existing training and development practices need to be resolved to reduce front-line employee turnover within an organization. The strategies within this paper support leaders through the LEAD: Listen, Explore, Act and Develop, Change Management Model. The LEAD Change Management Model supports the change process. This research proposes three possible solutions to improve an employee who is transferring between departments. The best solution to resolve the problem of improving an employee moving between departments experience is creating a Training Manager position within the retail store. A Training Manager position could support both employees and leadership with training and development of staff who are moving between departments. Within this research, an implementation plan using the TransX Model was created. The TransX Model is a hybrid of Leader-Member Exchange Theory and Transformational Leadership Theory to facilitate this organizational change within an organization by creating a common vision. Finally, this research provides the next steps as well as future considerations to enhance the training manager role within an organization.Keywords: employee transfers, employee engagement, human resources, employee induction, TransX model, lead change management model
Procedia PDF Downloads 491943 Organotin (IV) Based Complexes as Promiscuous Antibacterials: Synthesis in vitro, in Silico Pharmacokinetic, and Docking Studies
Authors: Wajid Rehman, Sirajul Haq, Bakhtiar Muhammad, Syed Fahad Hassan, Amin Badshah, Muhammad Waseem, Fazal Rahim, Obaid-Ur-Rahman Abid, Farzana Latif Ansari, Umer Rashid
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Five novel triorganotin (IV) compounds have been synthesized and characterized. The tin atom is penta-coordinated to assume trigonal-bipyramidal geometry. Using in silico derived parameters; the objective of our study is to design and synthesize promiscuous antibacterials potent enough to combat resistance. Among various synthesized organotin (IV) complexes, compound 5 was found as potent antibacterial agent against various bacterial strains. Further lead optimization of drug-like properties was evaluated through in silico predictions. Data mining and computational analysis were utilized to derive compound promiscuity phenomenon to avoid drug attrition rate in designing antibacterials. Xanthine oxidase and human glucose- 6-phosphatase were found as only true positive off-target hits by ChEMBL database and others utilizing similarity ensemble approach. Propensity towards a-3 receptor, human macrophage migration factor and thiazolidinedione were found as false positive off targets with E-value 1/4> 10^-4 for compound 1, 3, and 4. Further, displaying positive drug-drug interaction of compound 1 as uricosuric was validated by all databases and docked protein targets with sequence similarity and compositional matrix alignment via BLAST software. Promiscuity of the compound 5 was further confirmed by in silico binding to different antibacterial targets.Keywords: antibacterial activity, drug promiscuity, ADMET prediction, metallo-pharmaceutical, antimicrobial resistance
Procedia PDF Downloads 4761942 Ultrasound Enhanced Release of Active Targeting Liposomes Used for Cancer Treatment
Authors: Najla M. Salkho, Vinod Paul, Pierre Kawak, Rute F. Vitor, Ana M. Martin, Nahid Awad, Mohammad Al Sayah, Ghaleb A. Husseini
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Liposomes are popular lipid bilayer nanoparticles that are highly efficient in encapsulating both hydrophilic and hydrophobic therapeutic drugs. Liposomes promote a low risk controlled release of the drug avoiding the side effects of the conventional chemotherapy. One of the great potentials of liposomes is the ability to attach a wide range of ligands to their surface producing ligand-mediated active targeting of cancer tumour with limited adverse off-target effects. Ultrasound can also aid in the controlled and specified release of the drug from the liposomes by breaking it apart and releasing the drug in the specific location where the ultrasound is applied. Our research focuses on the synthesis of PEGylated liposomes (contain poly-ethylene glycol) encapsulated with the model drug calcein and studying the effect of low frequency ultrasound applied at different power densities on calcein release. In addition, moieties are attached to the surface of the liposomes for specific targeting of the cancerous cells which over-express the receptors of these moieties, ultrasound is then applied and the release results are compared with the moiety free liposomes. The results showed that attaching these moieties to the surface of the PEGylated liposomes not only enhance their active targeting but also stimulate calcein release from these liposomes.Keywords: active targeting, liposomes, moieties, ultrasound
Procedia PDF Downloads 5681941 Privacy Protection Principles of Omnichannel Approach
Authors: Renata Mekovec, Dijana Peras, Ruben Picek
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The advent of the Internet, mobile devices and social media is revolutionizing the experience of retail customers by linking multiple sources through various channels. Omnichannel retailing is a retailing that combines multiple channels to allow customers to seamlessly leverage all the distribution information online and offline while shopping. Therefore, today data are an asset more critical than ever for all organizations. Nonetheless, because of its heterogeneity through platforms, developers are currently facing difficulties in dealing with personal data. Considering the possibilities of omnichannel communication, this paper presents channel categorization that could enhance the customer experience of omnichannel center called hyper center. The purpose of this paper is fundamentally to describe the connection between the omnichannel hyper center and the customer, with particular attention to privacy protection. The first phase was finding the most appropriate channels of communication for hyper center. Consequently, a selection of widely used communication channels has been identified and analyzed with regard to the effect requirements for optimizing user experience. The evaluation criteria are divided into 3 groups: general, user profile and channel options. For each criterion the weight of importance for omnichannel communication was defined. The most important thing was to consider how the hyper center can make user identification while respecting the privacy protection requirements. The study carried out also shows what customer experience across digital networks would look like, based on an omnichannel approach owing to privacy protection principles.Keywords: personal data, privacy protection, omnichannel communication, retail
Procedia PDF Downloads 1131940 Ministers of Parliament and Their Official Web Sites; New Media Tool of Political Communication
Authors: Wijayanada Rupasinghe, A. H. Dinithi Jayasekara
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In a modern democracy, new media can be used by governments to involve citizens in decision-making, and by civil society to engage people in specific issues. However new media can also be used to broaden political participation by helping citizens to communicate with their representatives and with each other. Arguably this political communication is most important during election campaigns when political parties and candidates seek to mobilize citizens and persuade them to vote for a given party or candidate. The new media must be used by Parliaments, Parliamentarians, governments and political parties as they are highly effective tools to involve and inform citizens in public policymaking and in the formation of governments. But all these groups must develop strategies to deal with a wide array of both positive and negative effects of these rapidly growing media.New media has begun to take precedent over other communication outlets in part because of its heightened accessibility and usability. Using personal website can empower the public in a way that is far faster, cheaper and more pervasive than other forms of communication. They encourage pluralism, reach young people more than other media and encourage greater participation, accountability and transparency. This research discusses the impact politicians’ personal websites has over their overall electability and likability and explores the integration of website is an essential campaign tactic on both the local and national level. This research examined the impact of having personal website have over the way constituents view politicians. This research examined how politicians can use their website in the most effective fashion and incorporate these new media outlets as essential campaign tools and tactics. A mixed-method approach using content analysis. Content analysis selected thirty websites in sri Lankan politicians. Research revealed that politician’s new media usage significantly influenced and enriched the experience an individual has with the public figure.Keywords: election campaign ministers, new media, parliament, politicians websites
Procedia PDF Downloads 3401939 Analyses of Adverse Drug Reactions Reported of Hospital in Taiwan
Authors: Yu-Hong Lin
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Background: An adverse drug reaction (ADR) reported is an injury which caused by taking medicines. Sometimes the severity of ADR reported may be minor, but sometimes it could be a life-threatening situation. In order to provide healthcare professionals as a better reference in clinical practice, we do data collection and analysis from our hospital. Methods: This was a retrospective study of ADRs reported performed from 2014 to 2015 in our hospital in Taiwan. We collected assessment items of ADRs reported, which contain gender and age, occurring sources, Anatomical Therapeutic Chemical (ATC) classification of suspected drugs, types of adverse reactions, Naranjo score calculating by Naranjo Adverse Drug Reaction Probability Scale and so on. Results: The investigation included two hundred and seven ADRs reported. Most of ADRs reported were occurring in outpatient department (92%). The average age of ADRs reported was 65.3 years. Less than 65 years of age were in the majority in this study (54%). Majority of all ADRs reported were males (51%). According to ATC classification system, the major classification of suspected drugs was cardiovascular system (19%) and antiinfectives for systemic use (18%) respectively. Among the adverse reactions, Dermatologic Effects (35%) were the major type of ADRs. Also, the major Naranjo scores of all ADRs reported ranged from 1 to 4 points (91%), which represents a possible correlation between ADRs reported and suspected drugs. Conclusions: Definitely, ADRs reported is still an extremely important information for healthcare professionals. For that reason, we put all information of ADRs reported into our hospital's computer system, and it will improve the safety of medication use. By hospital's computer system, it can remind prescribers to think of information about patient's ADRs reported. No drugs are administered without risk. Therefore, all healthcare professionals should have a responsibility to their patients, who themselves are becoming more aware of problems associated with drug therapy.Keywords: adverse drug reaction, Taiwan, healthcare professionals, safe use of medicines
Procedia PDF Downloads 2061938 Development and Optimization of Colon Targeted Drug Delivery System of Ayurvedic Churna Formulation Using Eudragit L100 and Ethyl Cellulose as Coating Material
Authors: Anil Bhandari, Imran Khan Pathan, Peeyush K. Sharma, Rakesh K. Patel, Suresh Purohit
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The purpose of this study was to prepare time and pH dependent release tablets of Ayurvedic Churna formulation and evaluate their advantages as colon targeted drug delivery system. The Vidangadi Churna was selected for this study which contains Embelin and Gallic acid. Embelin is used in Helminthiasis as therapeutic agent. Embelin is insoluble in water and unstable in gastric environment so it was formulated in time and pH dependent tablets coated with combination of two polymers Eudragit L100 and ethyl cellulose. The 150mg of core tablet of dried extract and lactose were prepared by wet granulation method. The compression coating was used in the polymer concentration of 150mg for both the layer as upper and lower coating tablet was investigated. The results showed that no release was found in 0.1 N HCl and pH 6.8 phosphate buffers for initial 5 hours and about 98.97% of the drug was released in pH 7.4 phosphate buffer in total 17 hours. The in vitro release profiles of drug from the formulation could be best expressed first order kinetics as highest linearity (r2= 0.9943). The results of the present study have demonstrated that the time and pH dependent tablets system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of Embelin and Gallic acid for treatment of Helminthiasis.Keywords: embelin, gallic acid, Vidangadi Churna, colon targeted drug delivery
Procedia PDF Downloads 3331937 Determining Face-Validity for a Set of Preventable Drug-Related Morbidity Indicators Developed for Primary Healthcare in South Africa
Authors: D. Velayadum, P. Sthandiwe , N. Maharaj, T. Munien, S. Ndamase, G. Zulu, S. Xulu, F. Oosthuizen
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Introduction and aims of the study: It is the responsibility of the pharmacist to manage drug-related problems in order to ensure the greatest benefit to the patient. In order to prevent drug-related morbidity, pharmacists should be aware of medicines that may contribute to certain drug-related problems due to their pharmacological action. In an attempt to assist healthcare practitioners to prevent drug-related morbidity (PDRM), indicators for prevention have been designed. There are currently no indicators available for primary health care in developing countries like South Africa, where the majority of the population access primary health care. There is, therefore, a need to develop such indicators, specifically with the aim of assisting healthcare practitioners in primary health care. Methods: A literature study was conducted to compile a comprehensive list of PDRM indicators as developed internationally using the search engines Google Scholar and PubMed. MESH term used to retrieve suitable articles was 'preventable drug-related morbidity indicators'. The comprehensive list of PDRM indicators obtained from the literature study was further evaluated for face validity. Face validity was done in duplicate by 2 sets of independent researchers to ensure 1) no duplication of indicators when compiling a single list, 2) inclusion of only medication available in primary healthcare, and 3) inclusion of medication currently available in South Africa. Results: The list of indicators, compiled from PDRM indicators in the USA, UK, Portugal, Australia, India, and Canada contained 324 PDRM. 184 of these indicators were found to be duplicates, and the duplications were omitted, leaving a final list of 140. The 140 PDRM indicators were evaluated for face-validity, and 97 were accepted as relevant to primary health care in South Africa. 43 indicators did not comply with the criteria and were omitted from the final list. Conclusion: This study is a first step in compiling a list of PDRM indicators for South Africa. It is important to take cognizance to the fact the health systems differ vastly internationally, and it is, therefore, important to develop country-specific indicators.Keywords: drug-related morbidity, primary healthcare, South Africa, developing countries
Procedia PDF Downloads 1211936 Fabrication of Drug-Loaded Halloysite Nanotubes Containing Sodium Alginate/Gelatin Composite Scaffolds
Authors: Masoumeh Haghbin Nazarpak, Hamidreza Tolabi, Aryan Ekhlasi
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Bone defects are mentioned as one of the most challenging clinical conditions, affecting millions of people each year. A fracture, osteoporosis, tumor, or infection usually causes these defects. At present, autologous and allogeneic grafts are used to correct bone defects, but these grafts have some difficulties, such as limited access, infection, disease transmission, and immune rejection. Bone tissue engineering is considered a new strategy for repairing bone defects. However, problems with scaffolds’ design with unique structures limit their clinical applications. In addition, numerous in-vitro studies have been performed on the behavior of bone cells in two-dimensional environments. Still, cells grow in physiological situations in the human body in a three-dimensional environment. As a result, the controlled design of porous structures with high structural complexity and providing the necessary flexibility to meet specific needs in bone tissue repair is beneficial. For this purpose, a three-dimensional composite scaffold based on gelatin and sodium alginate hydrogels is used in this research. In addition, the antibacterial drug-loaded halloysite nanotubes were introduced into the hydrogel scaffold structure to provide a suitable substrate for controlled drug release. The presence of halloysite nanotubes improved hydrogel’s properties, while the drug eliminated infection and disease transmission. Finally, it can be acknowledged that the composite scaffold prepared in this study for bone tissue engineering seems promising.Keywords: halloysite nanotubes, bone tissue engineering, composite scaffold, controlled drug release
Procedia PDF Downloads 231935 Drug Delivery Nanoparticles of Amino Acid Based Biodegradable Polymers
Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava
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Nanosized environmentally responsive materials are of special interest for various applications, including targeted drug to a considerable potential for treatment of many human diseases. The important technological advantages of nanoparticles (NPs) usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic (water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. As the next step of this research an evaluation of biocompatibility and bioavailability of the synthesized NPs has been performed, using two stable human cell culture lines – HeLa and A549. This part of study is still in progress now.Keywords: amino acids, biodegradable polymers, nanoparticles (NPs), non-toxic building blocks
Procedia PDF Downloads 4091934 A Mathematical Analysis of Behavioural Epidemiology: Drugs Users Transmission Dynamics Based on Level Education for Susceptible Population
Authors: Firman Riyudha, Endrik Mifta Shaiful
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The spread of drug users is one kind of behavioral epidemiology that becomes a threat to every country in the world. This problem caused various crisis simultaneously, including financial or economic crisis, social, health, until human crisis. Most drug users are teenagers at school age. A new deterministic model would be constructed to determine the dynamics of the spread of drug users by considering level of education in a susceptible population. Based on the analytical model, two equilibria points were obtained; there were E₀ (zero user) and E₁ (endemic equilibrium). Existence of equilibrium and local stability of equilibria depended on the Basic Reproduction Ratio (R₀). This parameter was defined as the expected rate of secondary prevalence and primary prevalence in virgin population along spreading primary prevalence. The zero-victim equilibrium would be locally asymptotically stable if R₀ < 1 while if R₀ > 1 the endemic equilibrium would be locally asymptotically stable. The result showed that R₀ was proportional to the rate of interaction of each susceptible population based on educational level with the users' population. It is concluded that there was a need to be given a control in interaction, so that drug users population could be minimized. Numerical simulations were also provided to support analytical results.Keywords: drugs users, level education, mathematical model, stability
Procedia PDF Downloads 4501933 Learners’ Violent Behaviour and Drug Abuse as Major Causes of Tobephobia in Schools
Authors: Prakash Singh
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Many schools throughout the world are facing constant pressure to cope with the violence and drug abuse of learners who show little or no respect for acceptable and desirable social norms. These delinquent learners tend to harbour feelings of being beyond reproach because they strongly believe that it is well within their rights to engage in violent and destructive behaviour. Knives, guns, and other weapons appear to be more readily used by them on the school premises than before. It is known that learners smoke, drink alcohol, and use drugs during school hours, hence, their ability to concentrate, work, and learn, is affected. They become violent and display disruptive behaviour in their classrooms as well as on the school premises, and this atrocious behaviour makes it possible for drug dealers and gangsters to gain access onto the school premises. The primary purpose of this exploratory quantitative study was therefore to establish how tobephobia (TBP), caused by school violence and drug abuse, affects teaching and learning in schools. The findings of this study affirmed that poor discipline resulted in producing poor quality education. Most of the teachers in this study agreed that educating learners who consumed alcohol and other drugs on the school premises resulted in them suffering from TBP. These learners are frequently abusive and disrespectful, and resort to violence to seek attention. As a result, teachers feel extremely demotivated and suffer from high levels of anxiety and stress. The word TBP will surely be regarded as a blessing by many teachers throughout the world because finally, there is a word that will make people sit up and listen to their problems that cause real fear and anxiety in schools.Keywords: aims and objectives of quality education, debilitating effects of tobephobia, fear of failure associated with education, learners' violent behaviour and drug abuse
Procedia PDF Downloads 2551932 Formulation and Evaluation of Niosomes Containing an Antihypertensive Drug
Authors: Sunil Kamboj, Suman Bala, Vipin Saini
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Niosomes were formulated with an aim of enhancing the oral bioavailability of losartan potassium and formulated in different molar ratios of surfactant, cholesterol and dicetyl phosphate. The formulated niosomes were found in range of 54.98 µm to 107.85 µm in size. Formulations with 1:1 ratio of surfactant and cholesterol have shown maximum entrapment efficiencies. Niosomes with sorbitan monostearate showed maximum drug release and zero order release kinetics, at the end of 24 hours. The in vivo study has shown the significant enhancement in oral bioavailability of losartan potassium in rats, after a dose of 10 mg/kg. The average relative bioavailability in relation with pure drug solution was found 2.56, indicates more than two fold increase in oral bioavailability. A significant increment in MRT reflects the release retarding ability of the vesicles. In conclusion, niosomes could be a promising delivery of losartan potassium with improved oral bioavailability and prolonged release profiles.Keywords: non-ionic surfactant vesicles, losartan potassium, oral bioavailability, controlled release
Procedia PDF Downloads 3231931 Drug Design Modelling and Molecular Virtual Simulation of an Optimized BSA-Based Nanoparticle Formulation Loaded with Di-Berberine Sulfate Acid Salt
Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed
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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX
Procedia PDF Downloads 1451930 A Photoredox (C)sp³-(C)sp² Coupling Method Comparison Study
Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre
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Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods
Procedia PDF Downloads 1101929 Development and Characterization of Controlled Release Photo Cross-Linked Implants for Ocular Delivery of Triamcinolone Acetonide
Authors: Ravi Sheshala, Annie Lee, Ai Lin Ong, Ling Ling Cheu, Thiagarajan Madheswaran, Thankur R. R. Singh
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The objectives of the present research work were to develop and characterize biodegradable controlled release photo cross-linked implants of Triamcinolone Acetonide (TA) for the treatment of chronic ocular diseases. The photo cross-linked implants were prepared using film casting technique by mixing TA (2.5%) polyethylene glycol diacrylate (PEGDA 700), pore formers (mannitol, maltose, and gelatin) and the photoinitiator (Irgacure 2959). The resulting mixture was injected into moulds using 21 G and subjected to photocrosslinking at 365 nm. Scanning electron microscopy results demonstrated that more pores were formed in the films with the increase in the concentration of pore formers from 2%-10%. The maximum force required to break the films containing 2-10% of pore formers were determined in both dry and wet conditions using texture analyzer and found that films in a dry condition required a higher force to break compared to wet condition and blank films. In vitro drug release from photo cross-linked films were determined by incubating samples in 50 ml PBS pH 7.4 at 37 C and the samples were analyzed for drug release by HPLC. The films demonstrated a biphasic release profile i.e. an initial burst release (<20%) on the first day followed by a constant and continuous drug release in a controlled manner for 42 days. The drug release from all formulations followed the first-order release pattern and the combination of diffusion and erosion release mechanism. In conclusion, the developed formulations were able to provide controlled drug delivery to treat the chronic ocular diseases.Keywords: controlled release, ophthalmic, PEGDA, photocrosslinking, pore formers
Procedia PDF Downloads 3711928 Regular or Irregular: An Investigation of Medicine Consumption Pattern with Poisson Mixture Model
Authors: Lichung Jen, Yi Chun Liu, Kuan-Wei Lee
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Fruitful data has been accumulated in database nowadays and is commonly used as support for decision-making. In the healthcare industry, hospital, for instance, ordering pharmacy inventory is one of the key decision. With large drug inventory, the current cost increases and its expiration dates might lead to future issue, such as drug disposal and recycle. In contrast, underestimating demand of the pharmacy inventory, particularly standing drugs, affects the medical treatment and possibly hospital reputation. Prescription behaviour of hospital physicians is one of the critical factor influencing this decision, particularly irregular prescription behaviour. If a drug’s usage amount in the month is irregular and less than the regular usage, it may cause the trend of subsequent stockpiling. On the contrary, if a drug has been prescribed often than expected, it may result in insufficient inventory. We proposed a hierarchical Bayesian mixture model with two components to identify physicians’ regular/irregular prescription patterns with probabilities. Heterogeneity of hospital is considered in our proposed hierarchical Bayes model. The result suggested that modeling the prescription patterns of physician is beneficial for estimating the order quantity of medication and pharmacy inventory management of the hospital. Managerial implication and future research are discussed.Keywords: hierarchical Bayesian model, poission mixture model, medicines prescription behavior, irregular behavior
Procedia PDF Downloads 1021927 Enhanced Kinetic Solubility Profile of Epiisopiloturine Solid Solution in Hipromellose Phthalate
Authors: Amanda C. Q. M. Vieira, Cybelly M. Melo, Camila B. M. Figueirêdo, Giovanna C. R. M. Schver, Salvana P. M. Costa, Magaly A. M. de Lyra, Ping I. Lee, José L. Soares-Sobrinho, Pedro J. Rolim-Neto, Mônica F. R. Soares
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Epiisopiloturine (EPI) is a drug candidate that is extracted from Pilocarpus microphyllus and isolated from the waste of Pilocarpine. EPI has demonstrated promising schistosomicidal, leishmanicide, anti-inflammatory and antinociceptive activities, according to in vitro studies that have been carried out since 2009. However, this molecule shows poor aqueous solubility, which represents a problem for the release of the drug candidate and its absorption by the organism. The purpose of the present study is to investigate the extent of enhancement of kinetic solubility of a solid solution (SS) of EPI in hipromellose phthalate HP-55 (HPMCP), an enteric polymer carrier. SS was obtained by the solvent evaporation methodology, using acetone/methanol (60:40) as solvent system. Both EPI and polymer (drug loading 10%) were dissolved in this solvent until a clear solution was obtained, and then dried in oven at 60ºC during 12 hours, followed by drying in a vacuum oven for 4 h. The results show a considerable modification in the crystalline structure of the drug candidate. For instance, X-ray diffraction (XRD) shows a crystalline behavior for the EPI, which becomes amorphous for the SS. Polarized light microscopy, a more sensitive technique than XRD, also shows completely absence of crystals in SS sample. Differential Scanning Calorimetric (DSC) curves show no signal of EPI melting point in SS curve, indicating, once more, no presence of crystal in this system. Interaction between the drug candidate and the polymer were found in Infrared microscopy, which shows a carbonyl 43.3 cm-1 band shift, indicating a moderate-strong interaction between them, probably one of the reasons to the SS formation. Under sink conditions (pH 6.8), EPI SS had its dissolution performance increased in 2.8 times when compared with the isolated drug candidate. EPI SS sample provided a release of more than 95% of the drug candidate in 15 min, whereas only 45% of EPI (alone) could be dissolved in 15 min and 70% in 90 min. Thus, HPMCP demonstrates to have a good potential to enhance the kinetic solubility profile of EPI. Future studies to evaluate the stability of SS are required to conclude the benefits of this system.Keywords: epiisopiloturine, hipromellose phthalate HP-55, pharmaceuticaltechnology, solubility
Procedia PDF Downloads 5881926 Patient-Reported Adverse Drug Reactions, Medication Adherence and Clinical Outcomes among major depression disorder Patients in Ethiopia: A Prospective Hospital Based Study.
Authors: Tadesse Melaku Abegaz
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Background: there was paucity of data on the self-reported adverse drug reactions (ADRs), level of adherence and clinical outcomes with antidepressants among major depressive disorder (MDD) patients in Ethiopia. Hence, the present study sought to determine the level of adherence for and clinical outcome with antidepressants and the magnitude of ADRs. Methods: A prospective cross-sectional study was employed on MDD patients from September 2016 to January 2017 at Gondar university hospital psychiatry clinic. All patients who were available during the study period were included under the study population. The Naranjo adverse drug reaction probability scale was employed to assess the adverse drug reaction. The rate of medication adherence was determined using morisky medication adherence measurement scale eight. Clinical Outcome of patients was measured by using patient health questionnaire. Multivariable logistic carried out to determine factors for adherence and patient outcome. Results: two hundred seventy patients were participated in the study. More than half of the respondents were males 122(56.2%). The mean age of the participants was 30.94 ± 8.853. More than one-half of the subjects had low adherence to their medications 124(57.1%). About 186(85.7%) of patients encountered ADR. The most common ADR was weight gain 29(13.2). Around 198(92.2%) ADRs were probable and 19(8.8%) were possible. Patients with long standing MDD had high risk of non-adherence COR: 2.458[4.413-4.227], AOR: 2.424[1.185-4.961]. More than one-half 125(57.6) of respondents showed improved outcome. Optimal level of medication adherence was found to be associated with reduced risk of progression of the diseases COR: 0.37[0.110-5.379] and AOR: 0.432[0.201-0.909]. Conclusion: Patient reported adverse drug reactions were more prevalent in major depressive disorder patients. Adherence to medications was very poor in the setup. However, the clinical outcome was relatively higher. Long standing depression was associated with non-adherence. In addition, clinical outcome of patients were affected by non-adherence. Therefore, adherence enhancing interventions should be provided to improve medication adherence and patient outcome.Keywords: adverse drug reactions, clinical outcomes, Ethiopia, prospective study, medication adherence
Procedia PDF Downloads 2221925 Preparation and Size Control of Sub-100 Nm Pure Nanodrugs
Authors: Jinfeng Zhang, Chun-Sing Lee
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Pure nanodrugs (PNDs) – nanoparticles consisting entirely of drug molecules, have been considered as promising candidates for the next-generation nanodrugs. However, the traditional preparation method via reprecipitation faces critical challenges including low production rates, relatively large particle sizes and batch-to-batch variations. Here, for the first time, we successfully developed a novel, versatile and controllable strategy for preparing PNDs via an anodized aluminium oxide (AAO) template-assisted method. With this approach, we prepared PNDs of an anti-cancer drug (VM-26) with precisely controlled sizes reaching the sub-20 nm range. This template-assisted approach has much higher feasibility for mass production comparing to the conventional reprecipitation method and is beneficial for future clinical translation. The present method is further demonstrated to be easily applicable for a wide range of hydrophobic biomolecules without the need of custom molecular modifications and can be extended for preparing all-in-one nanostructures with different functional agents.Keywords: drug delivery, pure nanodrugs, size control, template
Procedia PDF Downloads 2781924 Simultaneous Determination of Proposed Anti-HIV Combination Comprising of Elvitegravir and Quercetin in Rat Plasma Using the HPLC–ESI-MS/MS Method: Drug Interaction Study
Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao
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Elvitegravir is the mainstay of anti-HIV combination therapy in most endemic countries presently. However, it cannot be used alone owing to its long onset time of action. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (Quercetin: QU) is a polyphenolic compound obtained from Argeria speciosa Linn (Family: Convolvulaceae), an anti-HIV candidate. In the present study, a sensitive, simple and rapid high-performance liquid chromatography coupled with positive ion electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination elvitegravir and Quercetin, in rat plasma. The method was linear over a range of 0.2–500 ng/ml. All validation parameters met the acceptance criteria according to regulatory guidelines. LC–MS/MS method for determination of Elvitegravir and Quercetin was developed and validated. Results show the potential of drug–drug interaction upon co-administration this marketed drugs and plant derived secondary metabolite.Keywords: anti-HIV resistance, extraction, HPLC-ESI-MS-MS, validation
Procedia PDF Downloads 3161923 Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy
Authors: Caroline Mendes, Mary McNamara, Orla Howe
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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers
Procedia PDF Downloads 283