Search results for: drug stability
Commenced in January 2007
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Edition: International
Paper Count: 5053

Search results for: drug stability

4963 Drug and Poison Information Centers: An Emergent Need of Health Care Professionals in Pakistan

Authors: Asif Khaliq, Sayeeda A. Sayed

Abstract:

The drug information centers provide drug related information to the requesters that include physicians, pharmacist, nurses and other allied health care professionals. The International Pharmacist Federation (FIP) describes basic functions of a drug and poison information centers as drug evaluation, therapeutic counseling, pharmaceutical advice, research, pharmaco-vigilence and toxicology. Continuous advancement in the field of medicine has expanded the medical literature, which has increased demand of a drug and poison information center for the guidance, support and facilitation of physicians. The objective of the study is to determine the need of drug and poison information centers in public and private hospitals of Karachi, Pakistan. A cross sectional study was conducted during July 2013 to April 2014 using a self-administered, multi-itemed questionnaire. Non Probability Convenient sampling was used to select the study participants. A total of 307 physicians from public and private hospitals of Karachi participated in the study. The need for 24/7 Drug and poison information center was highlighted by 92 % of physicians and 67% physicians suggested opening a drug information center at the hospital. It was reported that 70% physicians take at least 15 minutes for searching the information about the drug while managing a case. Regarding the poisoning case management, 52% physicians complaint about the unavailability of medicines in hospitals; and mentioned the importance of medicines for safe and timely management of patients. Although 73% physicians attended continued medical education (CME) sessions, 92 % physicians insisted on the need of 24/7 Drug and poison information center. The scarcity of organized channel for obtaining the information about drug and poisons is one of the most crucial problems for healthcare workers in Pakistan. The drug and poison information center is an advisory body that assists health care professional and patients in provision of appropriate drug and hazardous substance information. Drug and poison information center is one of the integral needs for running an effective health care system. Provision of a 24 /7 drug information centers with specialized staff offer multiple benefits to the hospitals while reducing treatment delays, addressing awareness gaps of all stakeholders and ensuring provision of quality health care.

Keywords: drug and poison information centers, Pakistan, physicians, public and private hospitals

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4962 Genetics of Pharmacokinetic Drug-Drug Interactions of Most Commonly Used Drug Combinations in the UK: Uncovering Unrecognised Associations

Authors: Mustafa Malki, Ewan R. Pearson

Abstract:

Tools utilized by health care practitioners to flag potential adverse drug reactions secondary to drug-drug interactions ignore individual genetic variation, which has the potential to markedly alter the severity of these interactions. To our best knowledge, there have been limited published studies on the impact of genetic variation on drug-drug interactions. Therefore, our aim in this project is the discovery of previously unrecognized, clinically important drug-drug-gene interactions (DDGIs) within the list of most commonly used drug combinations in the UK. The UKBB database was utilized to identify the top most frequently prescribed drug combinations in the UK with at least one route of interaction (over than 200 combinations were identified). We have recognised 37 common and unique interacting genes considering all of our drug combinations. Out of around 600 potential genetic variants found in these 37 genes, 100 variants have met the selection criteria (common variant with minor allele frequency ≥ 5%, independence, and has passed HWE test). The association between these variants and the use of each of our top drug combinations has been tested with a case-control analysis under the log-additive model. As the data is cross-sectional, drug intolerance has been identified from the genotype distribution as presented by the lower percentage of patients carrying the risky allele and on the drug combination compared to those free of these risk factors and vice versa with drug tolerance. In GoDARTs database, the same list of common drug combinations identified by the UKBB was utilized here with the same list of candidate genetic variants but with the addition of 14 new SNPs so that we have a total of 114 variants which have met the selection criteria in GoDARTs. From the list of the top 200 drug combinations, we have selected 28 combinations where the two drugs in each combination are known to be used chronically. For each of our 28 combinations, three drug response phenotypes have been identified (drug stop/switch, dose decrease, or dose increase of any of the two drugs during their interaction). The association between each of the three phenotypes belonging to each of our 28 drug combinations has been tested against our 114 candidate genetic variants. The results show replication of four findings between both databases : (1) Omeprazole +Amitriptyline +rs2246709 (A > G) variant in CYP3A4 gene (p-values and ORs with the UKBB and GoDARTs respectively = 0.048,0.037,0.92,and 0.52 (dose increase phenotype)) (2) Simvastatin + Ranitidine + rs9332197 (T > C) variant in CYP2C9 gene (0.024,0.032,0.81, and 5.75 (drug stop/switch phenotype)) (3) Atorvastatin + Doxazosin + rs9282564 (T > C) variant in ABCB1 gene (0.0015,0.0095,1.58,and 3.14 (drug stop/switch phenotype)) (4) Simvastatin + Nifedipine + rs2257401 (C > G) variant in CYP3A7 gene (0.025,0.019,0.77,and 0.30 (drug stop/switch phenotype)). In addition, some other non-replicated, but interesting, significant findings were detected. Our work also provides a great source of information for researchers interested in DD, DG, or DDG interactions studies as it has highlighted the top common drug combinations in the UK with recognizing 114 significant genetic variants related to drugs' pharmacokinetic.

Keywords: adverse drug reactions, common drug combinations, drug-drug-gene interactions, pharmacogenomics

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4961 Pattern of ICU Admission due to Drug Problems

Authors: Kamel Abd Elaziz Mohamed

Abstract:

Introduction: Drug related problems (DRPs) are of major concern, affecting patients of both sex. They impose considerable economic burden on the society and the health-care systems. Aim of the work: The aim of this work was to identify and categorize drug-related problems in adult intensive care unit. Patients and methods: The study was a prospective, observational study as eighty six patients were included. They were consecutively admitted to ICU through the emergency room or transferred from the general ward due to DRPs. Parameters included in the study as length of stay in ICU, need for cardiovascular support or mechanical ventilation, dialysis, as well as APACHE II score were recorded. Results: Drug related problems represent 3.6% of the total ICU admission. The median (range) of APACHE II score for 86 patients included in the study was 17 (10-23), and length of ICU stay was 2.4 (1.5-4.2) days. In 45 patients (52%), DRP was drug over dose (group 1), while other DRP was present in the other 41 patients (48%, group 11). Patients in group 1 were older (39 years versus 32 years in group 11), with significant impaired renal function. The need of inotropic drugs and mechanical ventilation as well as the length of stay (LOS) in ICU was significantly higher in group 1. There were no significant difference in GCS between both groups, however APACHE II score was significantly higher in group 1. Only four patients (4.6%) were admitted by suicidal attempt as well as three patients (3.4%) due to trauma drug-related admissions, all were in (group 1). Nineteen percent of the patients had drug related problem due to hypoglycaemic medication followed by tranquilizer (15%). Adverse drug effect followed by failure to receive medication were the most causes of drug problem in (group11).The total mortality rate was 4.6%, all of them were eventually non preventable. Conclusion: The critically ill patients admitted due to drug related problems represented a small proportion (3.6%) of admissions to the ICU. Hypoglycaemic medication was one of the most common causes of admission by drug related problems.

Keywords: drug related problems, ICU, cost, safety

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4960 The Effect of a Muscarinic Antagonist on the Lipase Activity

Authors: Zohreh Bayat, Dariush Minai-Tehrani

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Lipases constitute one of the most important groups of industrial enzymes that catalyze the hydrolysis of triacylglycerol to glycerol and fatty acids. Muscarinic antagonist relieves smooth muscle spasm of the gastrointestinal tract and effect on the cardiovascular system. In this research, the effect of a muscarinic antagonist on the lipase activity of Pseudomonas aeruginosa was studied. Lineweaver–Burk plot showed that the drug inhibited the enzyme by competitive inhibition. The IC50 value (60 uM) and Ki (30 uM) of the drug revealed the drug bound to the enzyme with high affinity. Determination of enzyme activity in various pH and temperature showed that the maximum activity of lipase was at pH 8 and 60°C both in presence and absence of the drug.

Keywords: bacteria, inhibition, kinetics, lipase

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4959 Drug-related Problems and Associated Factors among Adult Psychiatric Inpatients in Northwest Ethiopia: Multicenter Cross-Sectional Study

Authors: Ephrem Mebratu Dagnew, Mohammed Biset Ayalew, Gizework Alemnew Mekonnen, Alehegn Bishaw Geremew, Ousman Abubeker Abdela

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Objective: To assess the prevalence of drug-related problems and associated factors among adult psychiatric inpatients. Method: Hospital-based multicenter cross-sectional observational study was conducted from April to July 2021 at five randomly selected hospitals in North-west Ethiopia. A total of 325 consecutively sampled patients participated in the study. Clinical pharmacists assessed the DRPs based on clinical judgment supported by updated evidence-based diseases guidelines. A Medscape drug-interactions checker was used to check drug-drug interactions. The results were summarized using descriptive statistics, including frequency, mean, and standard deviation. Odds ratio (OR) with 95% confidence interval were also computed for each variable for the corresponding P-value. The value of P ≤ 0.05 was considered statistically significant. Result : From the total of 325 study participants, more than half of them (52.9%) were females and the mean age ± (standard deviation) was 30.8±11.3 years. At least one drug-related problem was recorded from 60.9%, 95% CI (55.7-65.8) of study participants with a mean of 0.6±0.49 per patient. Need additional drug therapy was the most common DRP (22.8%), followed by non-adherence to medicine (20.6%) and adverse drug reactions (11%), respectively. Factors independently associated with drug-related problems were rural residence [AOR=1.96,95%CI:1.01-2.84, P-value=0.046], self-employed [AOR=6.0 ,95% CI: 1.0-36.9, P-value=0.035] and alcohol drinkers [AOR=6.40,95%CI:1.12-37.5, p-value=0.034]. Conclusion: The prevalence of drug-related problems among adult psychiatric patients admitted to psychiatric wards was high. Healthcare providers give more attention to tackling these problems. Being a rural residence, self-employed, and Alcohol drinkers were associated with drug-related problems.

Keywords: psychiatric patients, drug-relatedproblems, multicenter, Ethiopia

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4958 Modeling of Drug Distribution in the Human Vitreous

Authors: Judith Stein, Elfriede Friedmann

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The injection of a drug into the vitreous body for the treatment of retinal diseases like wet aged-related macular degeneration (AMD) is the most common medical intervention worldwide. We develop mathematical models for drug transport in the vitreous body of a human eye to analyse the impact of different rheological models of the vitreous on drug distribution. In addition to the convection diffusion equation characterizing the drug spreading, we use porous media modeling for the healthy vitreous with a dense collagen network and include the steady permeating flow of the aqueous humor described by Darcy's law driven by a pressure drop. Additionally, the vitreous body in a healthy human eye behaves like a viscoelastic gel through the collagen fibers suspended in the network of hyaluronic acid and acts as a drug depot for the treatment of retinal diseases. In a completely liquefied vitreous, we couple the drug diffusion with the classical Navier-Stokes flow equations. We prove the global existence and uniqueness of the weak solution of the developed initial-boundary value problem describing the drug distribution in the healthy vitreous considering the permeating aqueous humor flow in the realistic three-dimensional setting. In particular, for the drug diffusion equation, results from the literature are extended from homogeneous Dirichlet boundary conditions to our mixed boundary conditions that describe the eye with the Galerkin's method using Cauchy-Schwarz inequality and trace theorem. Because there is only a small effective drug concentration range and higher concentrations may be toxic, the ability to model the drug transport could improve the therapy by considering patient individual differences and give a better understanding of the physiological and pathological processes in the vitreous.

Keywords: coupled PDE systems, drug diffusion, mixed boundary conditions, vitreous body

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4957 An Alternative Nano Design Strategy by Neutralized AMPS and Soy Bean Lecithin to Form Nanoparticles

Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu

Abstract:

Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.

Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS

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4956 Biophysical Analysis of the Interaction of Polymeric Nanoparticles with Biomimetic Models of the Lung Surfactant

Authors: Weiam Daear, Patrick Lai, Elmar Prenner

Abstract:

The human body offers many avenues that could be used for drug delivery. The pulmonary route, which is delivered through the lungs, presents many advantages that have sparked interested in the field. These advantages include; 1) direct access to the lungs and the large surface area it provides, and 2) close proximity to the blood circulation. The air-blood barrier of the alveoli is about 500 nm thick. The air-blood barrier consist of a monolayer of lipids and few proteins called the lung surfactant and cells. This monolayer consists of ~90% lipids and ~10% proteins that are produced by the alveolar epithelial cells. The two major lipid classes constitutes of various saturation and chain length of phosphatidylcholine (PC) and phosphatidylglycerol (PG) representing 80% of total lipid component. The major role of the lung surfactant monolayer is to reduce surface tension experienced during breathing cycles in order to prevent lung collapse. In terms of the pulmonary drug delivery route, drugs pass through various parts of the respiratory system before reaching the alveoli. It is at this location that the lung surfactant functions as the air-blood barrier for drugs. As the field of nanomedicine advances, the use of nanoparticles (NPs) as drug delivery vehicles is becoming very important. This is due to the advantages NPs provide with their large surface area and potential specific targeting. Therefore, studying the interaction of NPs with lung surfactant and whether they affect its stability becomes very essential. The aim of this research is to develop a biomimetic model of the human lung surfactant followed by a biophysical analysis of the interaction of polymeric NPs. This biomimetic model will function as a fast initial mode of testing for whether NPs affect the stability of the human lung surfactant. The model developed thus far is an 8-component lipid system that contains major PC and PG lipids. Recently, a custom made 16:0/16:1 PC and PG lipids were added to the model system. In the human lung surfactant, these lipids constitute 16% of the total lipid component. According to the author’s knowledge, there is not much monolayer data on the biophysical analysis of the 16:0/16:1 lipids, therefore more analysis will be discussed here. Biophysical techniques such as the Langmuir Trough is used for stability measurements which monitors changes to a monolayer's surface pressure upon NP interaction. Furthermore, Brewster Angle Microscopy (BAM) employed to visualize changes to the lateral domain organization. Results show preferential interactions of NPs with different lipid groups that is also dependent on the monolayer fluidity. Furthermore, results show that the film stability upon compression is unaffected, but there are significant changes in the lateral domain organization of the lung surfactant upon NP addition. This research is significant in the field of pulmonary drug delivery. It is shown that NPs within a certain size range are safe for the pulmonary route, but little is known about the mode of interaction of those polymeric NPs. Moreover, this work will provide additional information about the nanotoxicology of NPs tested.

Keywords: Brewster angle microscopy, lipids, lung surfactant, nanoparticles

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4955 Preparation and Characterization of Chitosan-Hydrocortisone Nanoshell for Drug Delivery Application

Authors: Suyeon Kwon, Ik Joong Kang, Wang Bingjie

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Chitosan is a polymer that is usually produced from N-deacetylation of chitin. It is emerging as a promising biocompatible polymer that is harmless to humans. For the reason that many merits such as good adsorptive, biodegradability, many researches are being done on the chitosan for drug delivery system. Drug delivery system (DDS) has been developed for the control of drug. It makes the drug can be delivered effectively and safely into the targeted human body. The drug used in this work is hydrocortisone that is used in Rheumatism, skin diseases, allergy treatment. In this work, hydrocortisone was used to make allergic rhinitis medicine. Our study focuses on drug delivery through the nasal mucosa by using hydrocortisone impregnated chitosan nanoshells. This study has performed an investigation in order to establish the optimal conditions, changing concentration, quantity of hydrocortisone. DLS, SEM, TEM, FT-IR, UV spectrum were used to analyze the manufactured chitosan-hydrocortisone silver nanoshell and silver nanoshell, whose function as drug carriers. This study has performed an investigation on new drug carriers and delivery routes for hydrocortisone. Various methods of manufacturing chitosan-hydrocortisone nanoshells were attempted in order to establish the optimal condition. As a result, the average size of chitosan-hydrocortisone silver nanoshell is about 80 nm. So, chitosan-hydrocortisone silver nanoshell is suitable as drug carriers because optimal size of drug carrier in human body is less than 120 nm. UV spectrum of Chitosan-hydrocortisone silver nanoshell shows the characteristic peak of silver nanoshell at 420 nm. Likewise, the average size of chitosan-hydrocortisone silver nanoshell is about 100nm. It is also suitable for drug carrier in human body. Also, multi-layered silver shell over chitosan nanoshells induced the red-shift of absorption peak and increased the intensity of absorption peak. The resultant chitosan–silver nanocomposites (or nanoshells) exhibited the absorption peak around 430nm attributed to silvershell formation. i.e. the absorption peak was red-shifted by ca. 40 nm in reference to 390 nm of silver nanoshells.

Keywords: chitosan, drug delivery, hydrocortisone, rhinitis, nanoshell

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4954 The Rational Design of Original Anticancer Agents Using Computational Approach

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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4953 Site-Specific Delivery of Hybrid Upconversion Nanoparticles for Photo-Activated Multimodal Therapies of Glioblastoma

Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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4952 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

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4951 Proniosomes as a Carrier for Ocular Drug Delivery

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

Abstract:

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

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

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4950 Global Stability Of Nonlinear Itô Equations And N. V. Azbelev's W-method

Authors: Arcady Ponosov., Ramazan Kadiev

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The work studies the global moment stability of solutions of systems of nonlinear differential Itô equations with delays. A modified regularization method (W-method) for the analysis of various types of stability of such systems, based on the choice of the auxiliaryequations and applications of the theory of positive invertible matrices, is proposed and justified. Development of this method for deterministic functional differential equations is due to N.V. Azbelev and his students. Sufficient conditions for the moment stability of solutions in terms of the coefficients for sufficiently general as well as specific classes of Itô equations are given.

Keywords: asymptotic stability, delay equations, operator methods, stochastic noise

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4949 In-silico Analysis of Plumbagin against Cancer Receptors

Authors: Arpita Roy, Navneeta Bharadvaja

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Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.

Keywords: cancer, receptor, plumbagin, docking

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4948 Atypical Retinoid ST1926 Nanoparticle Formulation Development and Therapeutic Potential in Colorectal Cancer

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

Abstract:

Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

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4947 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

Abstract:

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 589
4946 Charged Amphiphilic Polypeptide Based Micelle Hydrogel Composite for Dual Drug Release

Authors: Monika Patel, Kazuaki Matsumura

Abstract:

Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

Procedia PDF Downloads 181
4945 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

Abstract:

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 355
4944 Drug Delivery to Solid Tumor: Effect of Dynamic Capillary Network Induced by Tumor

Authors: Mostafa Sefidgar, Kaamran Raahemifar, Hossein Bazmara, Madjid Soltani

Abstract:

The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, and drug extravasation from microvascular. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to show how capillary network structure induced by tumor affects drug delivery. The effect of heterogeneous capillary network induced by tumor on interstitial fluid flow and drug delivery is investigated by this multi scale method. The sprouting angiogenesis model is used for generating capillary network induced by tumor. Fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network and fluid flow in normal and tumor tissues. The Starling’s law is used for closing this system of equations and coupling the intravascular and extravascular flows. Finally, convection-diffusion-reaction equation is used to simulate drug delivery. The dynamic approach which changes the capillary network structure based on signals sent by hemodynamic and metabolic stimuli is used in this study for more realistic assumption. The study indicates that drug delivery to solid tumors depends on the tumor induced capillary network structure. The dynamic approach generates the irregular capillary network around the tumor and predicts a higher interstitial pressure in the tumor region. This elevated interstitial pressure with irregular capillary network leads to a heterogeneous distribution of drug in the tumor region similar to in vivo observations. The investigation indicates that the drug transport properties have a significant role against the physiological barrier of drug delivery to a solid tumor.

Keywords: solid tumor, physiological barriers to drug delivery, angiogenesis, microvascular network, solute transport

Procedia PDF Downloads 286
4943 Sufficient Conditions for Exponential Stability of Stochastic Differential Equations with Non Trivial Solutions

Authors: Fakhreddin Abedi, Wah June Leong

Abstract:

Exponential stability of stochastic differential equations with non trivial solutions is provided in terms of Lyapunov functions. The main result of this paper establishes that, under certain hypotheses for the dynamics f(.) and g(.), practical exponential stability in probability at the small neighborhood of the origin is equivalent to the existence of an appropriate Lyapunov function. Indeed, we establish exponential stability of stochastic differential equation when almost all the state trajectories are bounded and approach a sufficiently small neighborhood of the origin. We derive sufficient conditions for exponential stability of stochastic differential equations. Finally, we give a numerical example illustrating our results.

Keywords: exponential stability in probability, stochastic differential equations, Lyapunov technique, Ito's formula

Procedia PDF Downloads 28
4942 Solubility Enhancement of Poorly Soluble Anticancer Drug, Docetaxel Using a Novel Polymer, Soluplus via Solid Dispersion Technique

Authors: Adinarayana Gorajana, Venkata Srikanth Meka, Sanjay Garg, Lim Sue May

Abstract:

This study was designed to evaluate and enhance the solubility of poorly soluble drug, docetaxel through solid dispersion (SD) technique prepared using freeze drying method. Docetaxel solid dispersions were formulated with Soluplus in different weight ratios. Freeze drying method was used to prepare the solid dispersions. Solubility of the solid dispersions were evaluated respectively and the optimized of drug-solubilizers ratio systems were characterized with different analytical methods like Differential scanning calorimeter (DSC), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) to confirm the formation of complexes between drug and solubilizers. The solubility data revealed an overall improvement in solubility for all SD formulations. The ternary combination 1:5:2 gave the highest increase in solubility that is approximately 3 folds from the pure drug, suggesting the optimum drug-solubilizers ratio system. This data corresponds with the DSC and SEM analyses, which demonstrates presence of drug in amorphous state and the dispersion in the solubilizers in molecular level. The solubility of the poorly soluble drug, docetaxel was enhanced through preparation of solid dispersion formulations employing freeze drying method. Solid dispersion with multiple carrier system shows better solubility compared to single carrier system.

Keywords: docetaxel, freeze drying, soluplus, solid dispersion technique

Procedia PDF Downloads 483
4941 Understanding Nanocarrier Efficacy in Drug Delivery Systems Using Molecular Dynamics

Authors: Maedeh Rahimnejad, Bahman Vahidi, Bahman Ebrahimi Hoseinzadeh, Fatemeh Yazdian, Puria Motamed Fath, Roghieh Jamjah

Abstract:

Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

Procedia PDF Downloads 267
4940 Mycobacterium tuberculosis and Molecular Epidemiology: An Overview

Authors: Asho Ali

Abstract:

Tuberculosis is a disease of grave concern which infects one-third of the global population. The high incidence of tuberculosis is further compounded by the increasing emergence of drug resistant strains including multi drug resistant (MDR). Global incidence MDR-TB is ~4%. Molecular epidemiological studies, based on the assumption that patients infected with clustered strains are epidemiologically linked, have helped understand the transmission dynamics of disease. It has also helped to investigate the basis of variation in Mycobacterium tuberculosis (MTB) strains, differences in transmission, and severity of disease or drug resistance mechanisms from across the globe. This has helped in developing strategies for the treatment and prevention of the disease including MDR.

Keywords: Mycobcaterium tuberculosis, molecular epidemiology, drug resistance, disease

Procedia PDF Downloads 371
4939 Green Synthesis (Using Environment Friendly Bacteria) of Silver-Nanoparticles and Their Application as Drug Delivery Agents

Authors: Sutapa Mondal Roy, Suban K. Sahoo

Abstract:

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 358
4938 Graph Clustering Unveiled: ClusterSyn - A Machine Learning Framework for Predicting Anti-Cancer Drug Synergy Scores

Authors: Babak Bahri, Fatemeh Yassaee Meybodi, Changiz Eslahchi

Abstract:

In the pursuit of effective cancer therapies, the exploration of combinatorial drug regimens is crucial to leverage synergistic interactions between drugs, thereby improving treatment efficacy and overcoming drug resistance. However, identifying synergistic drug pairs poses challenges due to the vast combinatorial space and limitations of experimental approaches. This study introduces ClusterSyn, a machine learning (ML)-powered framework for classifying anti-cancer drug synergy scores. ClusterSyn employs a two-step approach involving drug clustering and synergy score prediction using a fully connected deep neural network. For each cell line in the training dataset, a drug graph is constructed, with nodes representing drugs and edge weights denoting synergy scores between drug pairs. Drugs are clustered using the Markov clustering (MCL) algorithm, and vectors representing the similarity of drug pairs to each cluster are input into the deep neural network for synergy score prediction (synergy or antagonism). Clustering results demonstrate effective grouping of drugs based on synergy scores, aligning similar synergy profiles. Subsequently, neural network predictions and synergy scores of the two drugs on others within their clusters are used to predict the synergy score of the considered drug pair. This approach facilitates comparative analysis with clustering and regression-based methods, revealing the superior performance of ClusterSyn over state-of-the-art methods like DeepSynergy and DeepDDS on diverse datasets such as Oniel and Almanac. The results highlight the remarkable potential of ClusterSyn as a versatile tool for predicting anti-cancer drug synergy scores.

Keywords: drug synergy, clustering, prediction, machine learning., deep learning

Procedia PDF Downloads 45
4937 Hybrid-Nanoengineering™: A New Platform for Nanomedicine

Authors: Mewa Singh

Abstract:

Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.

Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals

Procedia PDF Downloads 459
4936 Core-Shell Type Magnetic Nanoparticles for Targeted Drug Delivery

Authors: Yogita Patil-Sen

Abstract:

Magnetic nanoparticles such as those made of iron oxide have been widely explored as biocatalysts, contrast agents, and drug delivery systems. However, some of the challenges associated with these particles are agglomeration and biocompatibility, which lead to concern of toxicity of the particles, especially for drug delivery applications. Coating the particles with biocompatible materials such as lipids and peptides have shown to improve the mentioned issues. Thus, these core-shell type nanoparticles are emerging as the new class of nanomaterials for targeted drug delivery applications. In this study, various types of core-shell magnetic nanoparticles are prepared and characterized using techniques, such as Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Vibrating Sample Magnetometer (VSM) and Thermogravimetric Analysis (TGA). The heating ability of nanoparticles is tested under oscillating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of oscillating field. The results suggest that the core-shell nanoparticles exhibit superparamagnetic behaviour, although, coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the oscillating magnetic field. Thus, the results strongly indicate the suitability of the prepared core-shell type nanoparticles as drug delivery vehicles and their potential in magnetic hyperthermia applications and for hyperthermia cancer therapy.

Keywords: core-shell, hyperthermia, magnetic nanoparticles, targeted drug delivery

Procedia PDF Downloads 309
4935 European Drug Serialization: Securing the Pharmaceutical Drug Supply Chain from Counterfeiters

Authors: Vikram Chowdhary, Marek Vins

Abstract:

The profitability of the pharmaceutical drug business has attracted considerable interest, but it also faces significant challenges. Counterfeiters take advantage of the industry's vulnerabilities, which are further exacerbated by the globalization of the market, online trading, and complex supply chains. Governments and organizations worldwide are dedicated to creating a secure environment that ensures a consistent and genuine supply of pharmaceutical products. In 2019, the European authorities implemented regulation EU 2016/161 to strengthen traceability and transparency throughout the entire drug supply chain. This regulation requires the addition of enhanced security features, such as serializing items to the saleable unit level or individual packs. Despite these efforts, the incidents of pharmaceutical counterfeiting continue to rise globally, with regulated territories being particularly affected. This paper examines the effectiveness of the drug serialization system implemented by European authorities. By conducting a systematic literature review, we assess the implementation of drug serialization and explore the potential benefits of integrating emerging digital technologies, such as RFID and Blockchain, to improve traceability and management. The objective is to fortify pharmaceutical supply chains against counterfeiters and manipulators and ensure their security.

Keywords: blockchain, counterfeit drugs, EU drug serialization, pharmaceutical industry, RFID

Procedia PDF Downloads 74
4934 Psycho-Social Issues: Drug Use and Abuse as a Social Problem among Secondary School Youths in Urban Centres of Benue State, Nigeria

Authors: Ode Kenneth Ogbu

Abstract:

This study was designed as a survey to investigate the incidence of use and abuse of drug as a social problem among the Nigeria youths in the secondary schools in urban centres of Benue state. 500 SS 3 and fresh secondary school graduates in remedial science class of Benue State University Makurdi with mean age of 16.8 were randomly sampled for the study. An instrument called drug use and abuse perception questionnaire (DAPQ) with a reliability coefficient of 74 were administered to the students. Only 337 copies of the questionnaire were properly completed and returned which reduced the sample size of 337. The data were subjected to factor analysis. X2 statistic and frequency distribution using split half method. The result of the analysis showed that: the DAPQ yield seven baseline factors responsible for drug use and abuse; there was appreciable evidence that the study subjects used drugs (42.1%); alcohol topped the list of the drugs consumed; most students use their pocket money to buy drugs; drugs were purchased from unconventional, hidden places and 13 out of the 20 items of DAPQ were perceived as significant factors in drug use and abuse. The paper recommends proper intervention of government, parents and NGO’S among students to reduce cases of drug abuse.

Keywords: drug abuse, psychology, psychiatry, students

Procedia PDF Downloads 280