Search results for: Intranasal drug delivery

Authors: Dolly Gadhiya, Jayvadan Patel, Mihir Raval

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Lercanidipine hydrochloride is a calcium channel blockers used for treating angina pectoris and hypertension. Lercanidipine is a BCS Class II drug having poor aqueous solubility. Absolute bioavailability of Lercanidipine is very low and the main reason ascribed for this is poor aqueous solubility of the drug. Design and formulatation of nanocrystals by media milling method was main focus of this study. In this present study preliminary optimization was carried out with one factor at a time (OFAT) approach. For this different parameters like size of milling beads, amount of zirconium beads, types of stabilizer, concentrations of stabilizer, concentrations of drug, stirring speeds and milling time were optimized on the basis of particle size, polydispersity index and zeta potential. From the OFAT model different levels for above parameters selected for Plackett - Burman Design (PBD). Plackett-Burman design having 13 runs involving 6 independent variables was carried out at higher and lower level. Based on statistical analysis of PBD it was found that concentration of stabilizer, concentration of drug and stirring speed have significant impact on particle size, PDI, zeta potential value and saturation solubility. These experimental designs for preparation of nanocrystals were applied successfully which shows increase in aqueous solubility and dissolution rate of Lercanidipine hydrochloride.

Keywords: Lercanidipine hydrochloride, nanocrystals, OFAT, Plackett Burman

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Authors: Ana Caroline Ibrahim Lino, Denise Bomtempo Birche de Carvalho

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The background of this research is the international process of control and monitoring of illicit psychoactive substances that has commenced in the early 20th century. This process was intensified with the UN Single Convention on Narcotic Drugs of 1961 and had its culmination in the 1970s with the "War on drugs", a doctrine undertaken by the United States of America. Since then, the phenomenon of drug prohibition has been pushing debates around alternatives of public policies to confront their consequences at a global level and in the specific context of Latin America. Previous research has answered the following key questions: a) With what characteristics and models has the international illicit drug control system consolidated in Latin America with the creation of the Organization of American States (OAS) and the Inter-American Drug Abuse Control Commission (CICAD)? b) What drug policies and programs were determined as guidelines for the member states by the OAS and CICAD? The present paper mainly addresses the analysis of the drug strategies developed by the OAS/CICAD for the Americas from 2004 to 2016. The primary sources have been extracted from the OAS/CICAD documents and reports, listed on the Internet sites of these organizations. Secondary sources refer to bibliographic research on the subject with the following descriptors: illicit drugs, public policies, international organizations, OAS, CICAD, and reducing the demand and supply of illicit drugs. The "content analysis" technique was used to organize the collected material and to choose the axes of analysis. The results show that the policies, strategies, and action plans for Latin America had been focused on anti-drug actions since the creation of the Commission until 2010. The discourses and policies to reduce drug demand and supply were of great importance for solving the problem. However, the real focus was on eliminating the substances by controlling the production, marketing, and distribution of illicit drugs. Little attention was given to the users and their families. The research is of great relevance to the Social Work. The guidelines and parameters of the Social Worker's profession are in line with the need for social, ethical, and political strengthening of any dimension that guarantees the rights of users of psychoactive substances. In addition, it contributed to the understanding of the political, economic, social, and cultural factors that structure the prohibitionism, whose matrix anchors the deprivation of rights and violence.

Keywords: illicit drug policies, international organizations, latin America, prohibitionism, reduce the demand and supply of illicit drugs

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Authors: Kobauri Sophio, Kantaria Tengiz, Tugushi David, Puiggali Jordi, Katsarava Ramaz

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Biodegradable biomaterials (BB) are of high interest for numerous applications in modern medicine as resorbable surgical materials and drug delivery systems. This kind of materials can be cleared from the body after the fulfillment of their function that excludes a surgical intervention for their removal. One of the most promising BBare amino acids based biodegradable poly(ester amide)s (PEAs) which are composed of naturally occurring (α-amino acids) and non-toxic building blocks such as fatty diols and dicarboxylic acids. Key bis-nucleophilic monomers for synthesizing the PEAs are diamine-diesters-di-p-toluenesulfonic acid salts of bis-(α-amino acid)-alkylenediesters (TAADs) which form the PEAs after step-growth polymerization (polycondensation) with bis-electrophilic counter-partners - activated diesters of dicarboxylic acids. The PEAs combine all advantages of the 'parent polymers' – polyesters (PEs) and polyamides (PAs): Ability of biodegradation (PEs), a high affinity with tissues and a wide range of desired mechanical properties (PAs). The scopes of applications of thePEAs can substantially be expanded by their functionalization, e.g. through the incorporation of hydrophobic fragments into the polymeric backbones. Hydrophobically modified PEAs can form non-covalent adducts with various compounds that make them attractive as drug carriers. For hydrophobic modification of the PEAs, we selected so-called 'Azlactone Method' based on the application of p-phenylene-bis-oxazolinons (bis-azlactones, BALs) as active bis-electrophilic monomers in step-growth polymerization with TAADs. Interaction of BALs with TAADs resulted in the PEAs with low MWs (Mw2,800-19,600 Da) and poor material properties. The high-molecular-weight PEAs (Mw up to 100,000) with desirable material properties were synthesized after replacement of a part of BALs with activated diester - di-p-nitrophenylsebacate, or a part of TAAD with alkylenediamine – 1,6-hexamethylenediamine. The new hydrophobically modified PEAs were characterized by FTIR, NMR, GPC, and DSC. It was shown that after the hydrophobic modification the PEAs retain the biodegradability (in vitro study catalyzed by α-chymptrypsin and lipase), and are of interest for constructing resorbable surgical and pharmaceutical devices including drug delivering containers such as microspheres. The new PEAs are insoluble in hydrophobic organic solvents such as chloroform or dichloromethane (swell only) that allowed elaborating a new technology of fabricating microspheres.

Keywords: amino acids, biodegradable polymers, bis-azlactones, microspheres

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Authors: S. Mohamed, D. Gonzalez, C. Sayada, P. Halfon

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Drug resistance mutations are routinely detected using standard Sanger sequencing, which does not detect minor variants with a frequency below 20%. The impact of detecting minor variants generated by ultra-deep sequencing (UDS) on HIV drug-resistance (DR) interpretations has not yet been studied. Fifty HIV-1 patients who experienced virological failure were included in this retrospective study. The HIV-1 UDS protocol allowed the detection and quantification of HIV-1 protease and reverse transcriptase variants related to genotypes A, B, C, E, F, and G. DeepChek®-HIV simplified DR interpretation software was used to compare Sanger sequencing and UDS. The total time required for the UDS protocol was found to be approximately three times longer than Sanger sequencing with equivalent reagent costs. UDS detected all of the mutations found by population sequencing and identified additional resistance variants in all patients. An analysis of DR revealed a total of 643 and 224 clinically relevant mutations by UDS and Sanger sequencing, respectively. Three resistance mutations with > 20% prevalence were detected solely by UDS: A98S (23%), E138A (21%) and V179I (25%). A significant difference in the DR interpretations for 19 antiretroviral drugs was observed between the UDS and Sanger sequencing methods. Y181C and T215Y were the most frequent mutations associated with interpretation differences. A combination of UDS and DeepChek® software for the interpretation of DR results would help clinicians provide suitable treatments. A cut-off of 1% allowed a better characterisation of the viral population by identifying additional resistance mutations and improving the DR interpretation.

Keywords: HIV-1, ultra-deep sequencing, Sanger sequencing, drug resistance

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Authors: Dagmara Malina, Katarzyna Bialik-Wąs, Klaudia Pluta

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The growing significance of transdermal systems, in which skin is a route for systemic drug delivery, has generated a considerable amount of data which has resulted in a deeper understanding of the mechanisms of transport across the skin in the context of the controlled and prolonged release of active substances. One of such solutions may be the use of carrier systems based on intelligent polymers with different physicochemical properties. In these systems, active substances, e.g. drugs, can be conjugated (attached), immobilized, or encapsulated in a polymer matrix that is sensitive to specific environmental conditions (e.g. pH or temperature changes). Intelligent polymers can be divided according to their sensitivity to specific environmental stimuli such as temperature, pH, light, electric, magnetic, sound, or electromagnetic fields. Materials & methods—The first stage of the presented research concerned the synthesis of pH-sensitive polymeric carriers by a radical polymerization reaction. Then, the selected active substance (hydrocortisone) was introduced into polymeric carriers. In a further stage, bio-hybrid sodium alginate/poly(vinyl alcohol) – SA/PVA-based hydrogel matrices modified with various carrier-drug systems were prepared with the chemical cross-linking method. The conducted research included the assessment of physicochemical properties of obtained materials i.e. degree of hydrogel swelling and degradation studies as a function of pH in distilled water and phosphate-buffered saline (PBS) at 37°C in time. The gel fraction represents the insoluble gel fraction as a result of inter-molecule cross-linking formation was also measured. Additionally, the chemical structure of obtained hydrogels was confirmed using FT-IR spectroscopic technique. The dynamic light scattering (DLS) technique was used for the analysis of the average particle size of polymer-carriers and carrier-drug systems. The nanocarriers morphology was observed using SEM microscopy. Results & Discussion—The analysis of the encapsulated polymeric carriers showed that it was possible to obtain the time-stable empty pH-sensitive carrier with an average size 479 nm and the encapsulated system containing hydrocortisone with an average 543 nm, which was introduced into hydrogel structure. Bio-hybrid hydrogel matrices are stable materials, and the presence of an additional component: pH-sensitive carrier – hydrocortisone system, does not reduce the degree of cross-linking of the matrix nor its swelling ability. Moreover, the results of swelling tests indicate that systems containing higher concentrations of the drug have a slightly higher sorption capacity in each of the media used. All analyzed materials show stable and statically changing swelling values in simulated body fluids - there is no sudden fluid uptake and no rapid release from the material. The analysis of FT-IR spectra confirms the chemical structure of the obtained bio-hybrid hydrogel matrices. In the case of modifications with a pH-sensitive carrier, a much more intense band can be observed in the 3200-3500 cm⁻¹ range, which most likely originates from the strong hydrogen interactions that occur between individual components.

Keywords: hydrogels, polymer nanocarriers, sodium alginate/poly(vinyl alcohol) matrices, wound dressings.

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Authors: Majid Farsadrooh, Mehran Feizi-Dehnayebi

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Serum albumin is the most abundant protein that is present in the circulatory system of a wide variety of organisms. Although it is a significant macromolecule, it can contribute to osmotic blood pressure and also, plays a superior role in drug disposition and efficiency. Molecular docking simulation can improve in silico drug design and discovery procedures to propound a lead compound and develop it from the discovery step to the clinic. In this study, the molecular docking simulation was applied to select a lead molecule through an investigation of the interaction of the two anticancer drugs (Alitretinoin and Abemaciclib) with Human Serum Albumin (HSA). Then, a series of new compounds (a-e) were suggested using lead molecule modification. Density functional theory (DFT) including MEP map and HOMO-LUMO analysis were used for the newly proposed compounds to predict the reactivity zones on the molecules, stability, and chemical reactivity. DFT calculation illustrated that these new compounds were stable. The estimated binding free energy (ΔG) values for a-e compounds were obtained as -5.78, -5.81, -5.95, -5,98, and -6.11 kcal/mol, respectively. Finally, the pharmaceutical properties and toxicity of these new compounds were estimated through OSIRIS DataWarrior software. The results indicated no risk of tumorigenic, irritant, or reproductive effects and mutagenicity for compounds d and e. As a result, compounds d and e, could be selected for further study as potential therapeutic candidates. Moreover, employing molecular docking simulation with the prediction of pharmaceutical properties helps to discover new potential drug compounds.

Keywords: drug design, anticancer, computational studies, DFT analysis

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Authors: Farah El Mohtadi, Richard d'Arcy, Nicola Tirelli

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Since 40 years, poly (ethylene glycol) (PEG) has been the gold standard in biomaterials and drug delivery, because of its combination of chemical and biological inertness. However, the possibility of its breakdown under oxidative conditions and the demonstrated development of anti-PEG antibodies highlight the necessity to develop carriers based on materials with increased stability in a challenging biological environment. Here, we describe the synthesis of polysulfide via anionic ring-opening polymerization. In vitro, the synthesized polymer was characterized by low toxicity and a level of complement activation (in human plasma) and macrophage uptake slightly lower than PEG and poly (2‐methyl-2‐oxazoline) (PMOX), of a similar size. Importantly, and differently from PEG, on activated macrophages, the synthesized polymer showed a strong and dose-dependent ROS scavenging activity, which resulted in the corresponding reduction of cytokine production. Therefore, the results from these studies show that polysulfide is highly biocompatible and are potential candidates to be used as an alternative to PEG for various applications in nanomedicine.

Keywords: PEG, low toxicity, ROS scavenging, biocompatible

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Authors: Afolabi O.J, Simon-Oke I.A., Oniya M.O., Okaka C.E.

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River blindness is a skin, and an eye disease caused by Onchocerca volvulus and vectored by a female hematophagous blackfly. The study aims to evaluate the distribution of the clinical signs of river blindness and the efficacy of ivermectin in the treatment of river blindness in Idogun. Observational studies in epidemiology that involve the use of a structured questionnaire to obtain useful epidemiological information from the respondents, physical assessment via palpation from head to ankle was used to assess clinical signs from the respondents and skin snip test was used to evaluate the prevalence of the disease. The efficacy of the drug was evaluated and expressed in percentages. One hundred and ninety-two (192) out of the 384 respondents examined, showed various signs of river blindness. However, it was only 108 (28.1%) respondents with the clinical signs that demonstrated Onchocerca volvulus microfilariae in their skin snips. The clinical signs observed among the respondents include skin depigmentation such as dermatitis, leopard skin, papules, pruritus and self-inflicted injury, while ocular symptoms include cataract, ocular lesion and partial blindness. Among these clinical signs, papules, and pruritus were the most dominant in the community. The prevalence of the clinical signs was observed to vary significantly among the age groups and gender (P<0.05). The efficacy of the drug after 6 and 12 months of treatments shows that the drug is more effective at age groups 10-50 years than the age groups 51-90 years. Ivermectin is observed to be efficacious in the treatment of the disease. However, to achieve eradication of the disease, the drug may be administered at 0.15mg/kg twice a year.

Keywords: riverblindness, clinical signs, ivermectin, Idogun

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Authors: J. Roberto Lopez, Hened Saade, Graciela Morales, Javier Enriquez, Raul G. Lopez

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Implementation of systems based on nanostructures for drug delivery applications have taken relevance in recent studies focused on biomedical applications. Although there are several nanostructures as drugs carriers, the use of polymeric nanoparticles (PNP) has been widely studied for this purpose, however, the main issue for these nanostructures is the size control below 50 nm with a narrow distribution size, due to they must go through different physiological barriers and avoid to be filtered by kidneys (< 10 nm) or the spleen (> 100 nm). Thus, considering these and other factors, it can be mentioned that drug-loaded nanostructures with sizes varying between 10 and 50 nm are preferred in the development and study of PNP/drugs systems. In this sense, the Semicontinuous Heterophase Polymerization (SHP) offers the possibility to obtain PNP in the desired size range. Considering the above explained, methacrylic copolymer nanoparticles were obtained under SHP. The reactions were carried out in a jacketed glass reactor with the required quantities of water, ammonium persulfate as initiator, sodium dodecyl sulfate/sodium dioctyl sulfosuccinate as surfactants, methyl methacrylate and methacrylic acid as monomers with molar ratio of 2/1, respectively. The monomer solution was dosed dropwise during reaction at 70 °C with a mechanical stirring of 650 rpm. Nanoparticles of poly(methyl methacrylate-co-methacrylic acid) were loaded with acetylsalicylic acid (ASA, aspirin) by a chemical adsorption technique. The purified latex was put in contact with a solution of ASA in dichloromethane (DCM) at 0.1, 0.2, 0.4 or 0.6 wt-%, at 35°C during 12 hours. According to the boiling point of DCM, as well as DCM and water densities, the loading process is completed when the whole DCM is evaporated. The hydrodynamic diameter was measured after polymerization by quasi-elastic light scattering and transmission electron microscopy, before and after loading procedures with ASA. The quantitative and qualitative analyses of PNP loaded with ASA were measured by infrared spectroscopy, differential scattering calorimetry and thermogravimetric analysis. Also, the molar mass distributions of polymers were determined in a gel permeation chromatograph apparatus. The load capacity and efficiency were determined by gravimetric analysis. The hydrodynamic diameter results for methacrylic PNP without ASA showed a narrow distribution with an average particle size around 10 nm and a composition methyl methacrylate/methacrylic acid molar ratio equal to 2/1, same composition of Eudragit S100, which is a commercial compound widely used as excipient. Moreover, the latex was stabilized in a relative high solids content (around 11 %), a monomer conversion almost 95 % and a number molecular weight around 400 Kg/mol. The average particle size in the PNP/aspirin systems fluctuated between 18 and 24 nm depending on the initial percentage of aspirin in the loading process, being the drug content as high as 24 % with an efficiency loading of 36 %. These average sizes results have not been reported in the literature, thus, the methacrylic nanoparticles here reported are capable to be loaded with a considerable amount of ASA and be used as a drug carrier.

Keywords: aspirin, biocompatibility, biodegradable, Eudragit S100, methacrylic nanoparticles

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Authors: V. Sathya Narayanan, P. Sidharth, V. R. Sanal Kumar

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The success of any retail business is predisposed by its swift response and its knack in understanding the constraints and the requirements of customers. In this paper a conceptual design model of an automated customer-friendly supermarket has been proposed. In this model a 10-sided, space benefited, regular polygon shaped gravity shelves have been designed for goods storage and effective customer-specific algorithms have been built-in for quick automatic delivery of the randomly listed goods. The algorithm is developed with two main objectives, viz., delivery time and priority. For meeting these objectives the randomly listed items are reorganized according to the critical-path of the robotic arm specific to the identified shop and its layout and the items are categorized according to the demand, shape, size, similarity and nature of the product for an efficient pick-up, packing and delivery process. We conjectured that the proposed automated supermarket model reduces business operating costs with much customer satisfaction warranting a win-win situation.

Keywords: automated supermarket, electronic shopping, polygon-shaped rack, shortest path algorithm for shopping

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Authors: Minwuyelet Maru, Solomon Habtemariam, Endalamaw Gadissa, Abraham Aseffa

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Background: Tuberculosis is a major public health problem in Ethiopia. The burden of TB is aggravated by emergence and expansion of drug resistant tuberculosis and different lineages of Mycobacterium tuberculosis (M. tuberculosis) have been reported in many parts of the country. Describing strains of Mycobacterial isolates and drug susceptibility pattern is necessary. Method: Sputum samples were collected from smear positive pulmonary TB patients age >= 7 years between October 1, 2012 to September 30, 2013 and Mycobacterial strains isolated on Loweensten Jensen (LJ) media. Each strain was characterized by deletion typing and Spoligotyping. Drug sensitivity testing was determined with the indirect proportion method using Middle brook 7H10 media and association to determine possible risk factors to drug resistance was done. Result: A total of 144 smear positive pulmonary tuberculosis patients were enrolled. The age of participants ranged from 7 to 78 with mean age of 29.22 (±10.77) years. In this study 82.2% (n=97) of the isolates were sensitive to the four first line anti-tuberculosis drugs and resistance to any of the four drugs tested was 17.8% (n=21). A high frequency of any resistance was observed in isoniazid, 13.6%, (n=16) followed by streptomycin, 11.8% (n=14). No significant association of isoniazid resistance with HIV, sex and history of previous TB treatment was observed but there was significant association with age, high between 31-35 years of age (p=0.01). Majority, 89.9% (n=128) of participants were new cases and only 11.1% (n=16) had history of previous TB treatment. No MDR-TB from new cases and 2 MDRTB (13.3%) was isolated from re-treatment cases which was significantly associated with previous TB treatment (p<0.01). Thirty two different types of spoligotype patterns were identified and 74.1% were grouped in to 13 clusters. The dominant strains were SIT 25, 18.1% (n=21), SIT 53, 17.2% (n=20) and SIT 149, 8.6% (n=10). Lineage 4 is the predominant lineage followed by lineage 3 and lineage 7 comprising 65.5% (n=76), 28.4% (n=33) and 6% (n=7) respectively. Majority of strains from lineage 3 and 4 were SIT 25 (63.6%) and SIT 53 (26.3%) whereas SIT 343 was the dominant strain from lineage 7 (71.4%). Conclusion: Wide spread of lineage 3 and lineage 4 of the modern lineage and high number of strain cluster indicates high ongoing transmission. The high proportion resistance to any of the first line anti-tuberculosis drugs may be a potential source in the emergence of MDR-TB. Wide spread of SIT 25 and SIT 53 having a tendency of ease transmission and presence of higher resistance of isoniazid in working and mobile age group, 31-35 years of age may increase risk of drug resistant strains transmission.

Keywords: tuberculosis, drug susceptibility, strain diversity, lineage, Ethiopia, spoligotyping

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Authors: Sheraz Gul

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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

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Authors: Kgabo H. Badimo, Sheryl Buckley

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Knowledge is increasingly recognised in this, the knowledge era, as a strategic resource, by public sector organisations, in view of the public sector reform initiatives. People and knowledge play a vital role in attaining improved organisational performance and high service quality. Many government departments in the public sector have started to realise the importance of knowledge management in streamlining their operations and processes. This study focused on knowledge management in the public healthcare service organisations, where the concept of service provider competitiveness pales to insignificance, considering the huge challenges emanating from the healthcare and public sector reforms. Many government departments are faced with challenges of improving organisational performance and service delivery, improving accountability, making informed decisions, capturing the knowledge of the aging workforce, and enhancing partnerships with stakeholders. The purpose of this paper is to examine the knowledge management practices of the Gauteng Department of Health in South Africa, in order to understand how knowledge management practices influence improvement in organisational performance and healthcare service delivery. This issue is explored through a review of literature on dominant views on knowledge management and healthcare service delivery, as well as results of interviews with, and questionnaire responses from, the general staff of the Gauteng Department of Health. Web-based questionnaires, face-to-face interviews and organisational documents were used to collect data. The data were analysed using both the quantitative and qualitative methods. The central question investigated was: To what extent can the conditions required for successful knowledge management be observed, in order to improve organisational performance and healthcare service delivery in the Gauteng Department of Health. The findings showed that the elements of knowledge management capabilities investigated in this study, namely knowledge creation, knowledge sharing and knowledge application, have a positive, significant relationship with all measures of organisational performance and healthcare service delivery. These findings thus indicate that by employing knowledge management principles, the Gauteng Department of Health could improve its ability to achieve its operational goals and objectives, and solve organisational and healthcare challenges, thereby improving organisational.

Keywords: knowledge management, Healthcare Service Delivery, public healthcare, public sector

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Authors: Ji-Chan Jang

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Tuberculosis is still major health problem because there is an increase of multidrug-resistant and extensively drug-resistant forms of the disease. Therefore, the most urgent clinical need is to discover potent agents and develop novel drug combination capable of reducing the duration of MDR and XDR tuberculosis therapy. Three reference strains H37Rv, CDC1551, W-Beijing GC1237 and six clinical isolates of MDRTB were tested to daptomycin in the range of 0.013 to 256 mg/L. Daptomycin is resistant to all tested M. tuberculosis strains not only laboratory strains but also clinical MDR strains that were isolated at different source. Daptomycin will not be an antibiotic of choice for treating infection of Gram positive atypical slowly growing M. tuberculosis.

Keywords: tuberculosis, daptomycin, resistance, Mycobacterium tuberculosis

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Authors: Samiah Rehman, Kashmira J. Gohil

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Objective: Dracaena trifascaita extract (DTE) possesses strong antioxidant and anti-inflammatory properties that play a vital role in the treatment of mental disorders like depression. The present study was designed to evaluate the antidepressant effects of hydroalcoholic extracts of DT on behavioral models of depression. Methodology: Animals were randomly divided into 6 groups of 5 each: Group 1 and 2 received distilled water and standard drug, imipramine: 25mg/kg, respectively. Groups 4, 5 and 6 received DTE treatment orally at doses of 200 ,400 and 600mg/ kg, respectively, for 14 days. Time of immobility was noted by force swimming test (FST)and tail suspension test (TST) on the 1st,7th and 14th days. Results: The time of immobility was reduced in the treatment group as compared to the control and standard. DTE600 mg/kg showed the highest and most significant antidepressant effects as compared to the standard drug imipramine. (25mg/kg). Conclusion: DTE has good potential as an alternative therapy for depression.

Keywords: Dracaena trifasciata, antidepressants, force swimming test, tail suspension test, herbal drug of depression

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Authors: Susan Amirsalari, Azime Khosrinejad, Elham Rahimian

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Objective: Epilepsy is a common brain disorder characterized by a persistent tendency to develop in neurological, cognitive, and psychological contents. Magnetic Resonance Imaging (MRI) is a neuroimaging test facilitating the detection of structural epileptogenic lesions. This study aimed to compare the MRI findings between patients with intractable and drug-responsive epilepsy. Material & methods: This case-control study was conducted from 2007 to 2019. The research population encompassed all 1-16- year-old patients with intractable epilepsy referred to the Shafa Neuroscience Center (n=72) (a case group) and drug-responsive patients referred to the pediatric neurology clinic of Baqiyatallah Hospital (a control group). Results: There were 72 (23.5%) patients in the intractable epilepsy group and 200 (76.5%) patients in the drug-responsive group. The participants' mean age was 6.70 ±4.13 years, and there were 126 males and 106 females in this study Normal brain MRI was noticed in 21 (29.16%) patients in the case group and 184 (92.46%) patients in the control group. Neuronal migration disorder (NMD)was also exhibited in 7 (9.72%) patients in the case group and no patient in the control group. There were hippocampal abnormalities and focal lesions (mass, dysplasia, etc.) in 10 (13.88%) patients in the case group and only 1 (0.05%) patient in the control group. Gliosis and porencephalic cysts were presented in 3 (4.16%) patients in the case group and no patient in the control group. Cerebral and cerebellar atrophy was revealed in 8 (11.11%) patients in the case group and 4 (2.01%) patients in the control group. Corpus callosum agenesis, hydrocephalus, brain malacia, and developmental cyst were more frequent in the case group; however, the difference between the groups was not significant. Conclusion: The MRI findings such as hippocampal abnormalities, focal lesions (mass, dysplasia), NMD, porencephalic cysts, gliosis, and atrophy are significantly more frequent in children with intractable epilepsy than in those with drug-responsive epilepsy.

Keywords: magnetic resonance imaging, intractable epilepsy, drug responsive epilepsy, neuronal migrational disorder

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

Procedia PDF Downloads 457

Authors: Neelam Rashid, Muhammad Zafar, Mushtaq Ahmad, Khafsa Malik, Syed Nasar Shah

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The present study was conducted to study the role of medicinal plants used to cure different ailments in Azad Kashmir. Various ethno medicinal surveys were carried out during 2016 to enlist the uses of plants against various ailments by rural communities of the area. Information was obtained from 60 local people including 45 males (10 traditional health practitioners) and 15 females by semi structured interviews and group discussions. 65 plant species belonging to 45 families were reported. The dominant plant habit was herbaceous (56%) while decoction was the most common method of utilization (40%). The most cited turmoil was the gastrointestinal disorders. The data obtained were analyzed using ethno medicinal indices such as FL, UV, ICF, FC, and RFC. Results revealed that various species had numerous uses in curing of diseases. So conservation of biodiversity of these medicinal plants and traditional knowledge can play important role in improving the local health conditions of rural people and modern drug discovery and development.

Keywords: medicinal plants, ailments, drug, health, traditional

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Authors: Alexis John de Britto

Abstract:

Studies were performed to select the superior genotypes based on intra-specific variations, caused by phytogeographical, climatic and edaphic parameters of three anti cancer drug yielding mangrove plants such as Acanthus ilicifolius L., Calophyllum inophyllum L. and Excoecaria agallocha L. using ISSR (Inter Simple Sequence Repeats) markers and phytochemical analysis such as preliminary phytochemical tests, TLC, HPTLC, HPLC and antioxidant tests. The plants were collected from five different geographical locations of the East Coast of south India. Genetic heterozygosity, Nei’s gene diversity, Shannon’s information index and Percentage of polymorphism between the populations were calculated using POPGENE software. Cluster analysis was performed using UPGMA algorithm. AMOVA and correlations between genetic diversity and soil factors were analyzed. Combining the molecular and phytochemical variations superior genotypes were selected. Conservation constraints and methods of efficient exploitation of the species are discussed.

Keywords: anti-cancer drug yielding plants, DNA fingerprinting, phytochemical analysis, selection of superior genotypes

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Authors: Jiahui Song, Ravindra P. Joshi

Abstract:

The use of high-intensity, short-duration electric pulses is a promising development with many biomedical applications. The uses include irreversible electroporation for killing abnormal cells, reversible poration for drug and gene delivery, neuromuscular manipulation, and the shrinkage of tumors, etc. High intensity, short-duration electric pulses result in the creation of high-density, nanometer-sized pores in the cellular membrane. This electroporation amounts to localized modulation of the transverse membrane conductance, and effectively provides a voltage shunt. The electrically controlled changes in the trans-membrane conductivity could be used to affect neural traffic and action potential propagation. A rat was taken as the representative example in this research. The simulation study shows the pathway from the sensorimotor cortex down to the spinal motoneurons, and effector muscles could be reversibly blocked by using high-intensity, short-duration electrical pulses. Also, actual experimental observations were compared against simulation predictions.

Keywords: action potential, electroporation, high-intensity, short-duration

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Authors: Dale Dzemydiene, Aurelija Burinskiene, Arunas Miliauskas, Kristina Ciziuniene

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Data flow and the purpose of reporting the data are different and dependent on business needs. Different parameters are reported and transferred regularly during freight delivery. This business practices form the dataset constructed for each time point and contain all required information for freight moving decisions. As a significant amount of these data is used for various purposes, an integrating methodological approach must be developed to respond to the indicated problem. The proposed methodology contains several steps: (1) collecting context data sets and data validation; (2) multi-objective analysis for optimizing freight transfer services. For data validation, the study involves Grubbs outliers analysis, particularly for data cleaning and the identification of statistical significance of data reporting event cases. The Grubbs test is often used as it measures one external value at a time exceeding the boundaries of standard normal distribution. In the study area, the test was not widely applied by authors, except when the Grubbs test for outlier detection was used to identify outsiders in fuel consumption data. In the study, the authors applied the method with a confidence level of 99%. For the multi-objective analysis, the authors would like to select the forms of construction of the genetic algorithms, which have more possibilities to extract the best solution. For freight delivery management, the schemas of genetic algorithms' structure are used as a more effective technique. Due to that, the adaptable genetic algorithm is applied for the description of choosing process of the effective transportation corridor. In this study, the multi-objective genetic algorithm methods are used to optimize the data evaluation and select the appropriate transport corridor. The authors suggest a methodology for the multi-objective analysis, which evaluates collected context data sets and uses this evaluation to determine a delivery corridor for freight transfer service in the multi-modal transportation network. In the multi-objective analysis, authors include safety components, the number of accidents a year, and freight delivery time in the multi-modal transportation network. The proposed methodology has practical value in the management of multi-modal transportation processes.

Keywords: multi-objective, analysis, data flow, freight delivery, methodology

Procedia PDF Downloads 180

Authors: Pei-Chun Chen, Chi-Ting Tseng, Lih-Chi Chen, Kai-Hsiang Yang

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Introduction: The pharmacist is responsible for encouraging adverse drug reaction (ADR) reporting. In a local center in Northern Taiwan, promotion and rewarding of ADR reporting have continued for over six years but failed to bring significant changes. This study aims to find a solution to increase ADR reporting. Research question or hypothesis: We hypothesized that under-reporting is due to the inconvenience of the reporting system. Reports were made conventionally through printed sheets. We proposed that reports made per month will increase if they were computerized. Study design: An ADR reporting platform was established in April 2015, before which was defined as the first stage of this study (January-March, 2015) and after which the second stage. The third stage commenced in November, 2015, after adding a reporting module to physicians prescription system. ADRs could be reported simultaneously when documenting drug allergies. Methods: ADR report rates during the three stages of the study were compared. Effects of the information platform on reporting were also analyzed. Results: During the first stage, the number of ADR reports averaged 6 per month. In the second stage, the number of reports per month averaged 1.86. Introducing the information platform had little effect on the monthly number of ADR reports. The average number of reports each month during the third stage of the study was 11±3.06, with 70.43% made electronically. Reports per month increased significantly after installing the reporting module in November, 2015 (P<0.001, t-test). In the first two stages, 29.03% of ADR reports were made by physicians, as compared to 70.42% of cases in the third stage of the study. Increased physician reporting possibly account for these differences. Conclusion: Adding a reporting module to the prescription system significantly increased ADR reporting. Improved accessibility is likely the cause. The addition of similar modules to computer systems of other healthcare professions may be considered to encourage spontaneous ADR reporting.

Keywords: adverse drug reactions, adverse drug reaction reporting systems, regional hospital, prescription system

Procedia PDF Downloads 351

Authors: Christi Jackson, Chuka Onaga

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Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

Procedia PDF Downloads 169

Authors: Sankarprasad Bhuniya, Sukhendu Maiti, Eun-Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

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A new theranostic strategy is described. It is based on the use of an “all in one” prodrug, namely the biotinylated piperazine-rhodol conjugate 4a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1a. This release is made selective as the result of the biotin functionality. Fluorophore 1a is 32-fold more fluorescent than prodrug 4a. It permits the delivery and release of the SN-38 payload to be monitored easily in vitro and in vivo, as inferred from cell studies and ex vivo analyses of mice xenografts derived HeLa cells, respectively. Prodrug 4a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy.

Keywords: theranostic, prodrug, cancer therapy, fluorescence

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Authors: Ahmed El-Fiqi, Hae-Won Kim

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Incorporation of therapeutic elements such as Sr, Cu and Co into bioglass structure and their release as ions is considered as one of the promising approaches to enhance cellular responses, e.g., osteogenesis and angiogenesis. Here, cobalt as angiogenesis promoter has been incorporated (at 0, 1 and 4 mol%) into sol-gel derived calcium silicate mesoporous bioglass nanoparticles. The composition and structure of cobalt-free (CFN) and cobalt-doped (CDN) mesoporous bioglass nanoparticles have been analyzed by X-ray fluorescence (XRF), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier-Transform Infra-red spectroscopy (FT-IR). The physicochemical properties of CFN and CDN have been investigated using high-resolution transmission electron microscopy (HR-TEM), Selected area electron diffraction (SAED), and Energy-dispersive X-ray (EDX). Furthermore, the textural properties, including specific surface area, pore-volume, and pore size, have been analyzed from N²⁻sorption analyses. Surface charges of CFN and CDN were also determined from surface zeta potential measurements. The release of ions, including Co²⁺, Ca²⁺, and SiO₄⁴⁻ has been analyzed using inductively coupled plasma atomic emission spectrometry (ICP-AES). Loading and release of diclofenac as an anti-inflammatory drug model were explored in vitro using Ultraviolet-visible spectroscopy (UV-Vis). XRD results ensured the amorphous state of CFN and CDN whereas, XRF further confirmed that their chemical compositions are very close to the designed compositions. HR-TEM analyses unveiled nanoparticles with spherical morphologies, highly mesoporous textures, and sizes in the range of 90 - 100 nm. Moreover, N²⁻ sorption analyses revealed that the nanoparticles have pores with sizes of 3.2 - 2.6 nm, pore volumes of 0.41 - 0.35 cc/g and highly surface areas in the range of 716 - 830 m²/g. High-resolution XPS analysis of Co 2p core level provided structural information about Co atomic environment and it confirmed the electronic state of Co in the glass matrix. ICP-AES analysis showed the release of therapeutic doses of Co²⁺ ions from 4% CDN up to 100 ppm within 14 days. Finally, diclofenac loading and release have ensured the drug/ion co-delivery capability of 4% CDN.

Keywords: mesoporous bioactive glass, nanoparticles, cobalt ions, release

Procedia PDF Downloads 107

Authors: Maninderjeet K. Grewal, Sakshi Bhatnor, Renu Chadha

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The composition of pharmaceutical entities and the molecular interactions can be altered to optimize drug properties such as solubility and bioavailability by the crystal engineering technique. The present work has emphasized on the preparation, characterization, and biopharmaceutical evaluation of co-crystal of BCS Class II anti-osteoarthritis drug, Oxaprozin (OXA) with aspartic acid (ASPA) as co-former. The co-crystals were prepared through the mechanochemical solvent drop grinding method. Characterization of the prepared co-crystal (OXA-ASPA) was done by using analytical tools such as differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD). DSC thermogram of OXA-ASPA cocrystal showed a single sharp melting endotherm at 235 ºC, which was between the melting peaks of the drug and the counter molecules suggesting the formation of a new phase which is a co-crystal that was further confirmed by using other analytical techniques. FT-IR analysis of OXA-ASPA cocrystal showed a shift in a hydroxyl, carbonyl, and amine peaks as compared to pure drugs indicating all these functional groups are participating in cocrystal formation. The appearance of new peaks in the PXRD pattern of cocrystals in comparison to individual components showed that a new crystalline entity has been formed. The Crystal structure of cocrystal was determined using material studio software (Biovia) from PXRD. The equilibrium solubility study of OXA-ASPA showed improvement in solubility as compared to pure drug. Therefore, it was envisioned to prepare the co-crystal of oxaprozin with a suitable conformer to modulate its physiochemical properties and consequently, the biopharmaceutical parameters.

Keywords: cocrystals, coformer, oxaprozin, solubility

Procedia PDF Downloads 115

Authors: Mostafa Ghasemi, Andrew Urquhart

Abstract:

In this study, fluorescent carbon dots (CDs) were synthesized in a green way using a one-step hydrothermal method. Carbon dots are carbon-based nanomaterials with a size of less than 10 nm, unique structure, and excellent properties such as low toxicity, good biocompatibility, tunable fluorescence, excellent photostability, and easy functionalization. These properties make them a good candidate to use in different fields such as biological sensing, photocatalysis, photodynamic, and drug delivery. Fourier transformed infrared (FTIR) spectra approved OH/NH groups on the surface of the as-synthesized CDs, and UV-vis spectra showed excellent fluorescence quenching effect of Fe (III) ion on the as-synthesized CDs with high selectivity detection compared with other metal ions. The probe showed a linear response concentration range (0–2.0 mM) to Fe (III) ion, and the limit of detection was calculated to be about 0.50 μM. In addition, CDs also showed good sensitivity to the pH value in the range from 2 to 14, indicating great potential as a pH sensor.

Keywords: carbon dots, fluorescence, pH sensing, metal ions sensor

Procedia PDF Downloads 75

Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Eda Cagli, Irem Erel Goktepe

Abstract:

Externally triggered and effective release of therapeutics from polymer nanoplatforms is one of the key issues in cancer treatment. In this study, we aim to prepare polymer multilayer films which are stable at physiological conditions (little or no drug release) but release drug molecules at acidic pH and via application of AC magnetic field. First, novel stimuli responsive diblock copolymers composed of pH- and temperature-responsive blocks were synthesized. Then, block copolymer micelles with pH-responsive core and temperature responsive coronae will be obtained via pH-induced self-assembly of these block copolymers in aqueous environment. A model anticancer drug, e.g. Doxorubicin will be loaded in the micellar cores. Second, superparamagnetic nanoparticles will be synthesized. Magnetic nanoparticles and drug loaded block copolymer micelles will be used as building blocks to construct the multilayers. To mimic the acidic nature of the tumor tissues, Doxorubicin release from the micellar cores will be induced at acidic conditions. Moreover, Doxorubicin release from the multilayers will be facilitated via magnetothermal trigger. Application of AC magnetic field will induce the heating of magnetic nanoparticles resulting in an increase in the temperature of the polymer platform. This increase in temperature is expected to trigger conformational changes on the temperature-responsive micelle coronae and facilitate the release of Doxorubicin from the surface. Such polymer platform may find use in biomedical applications.

Keywords: layer-by-layer films, magnetothermal trigger, smart polymers, stimuli responsive

Procedia PDF Downloads 364