Search results for: drug accessibility

Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri

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—Results The prudent administration of antibiotics aims to avoid the side effects and the microbes' resistance to antibiotics. An approach developing methods of local administration of antibiotics is especially required for localized infections caused by bacterial colonization of medical devices or implant materials. Among the wide variety of materials used as drug delivery systems, bioactive glasses (BG) have large utilization in regenerative medicine . firstly, the production of bioactive glass/nickel oxide/tin dioxide nanocomposite using sol-gel method, and then, the controlled release of imipenem from the double metal oxide/bioactive glass nanocomposite, and finally, the investigation of the antibacterial property of the nanocomposite. against a number of implant-related infectious agents. In this study, BG/SnO2 and BG/NiO single systema with different metal oxide present and BG/NiO/SnO2 nanocomposites were synthesized by sol-gel as drug carriers for tetracycline and imepinem. These two antibiotics were widely used for osteomyelitis because of its favorable penetration and bactericidal effect on all the probable osteomyelitis pathogens. The antibacterial activity of synthesized samples were evaluated against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa as bacteria model using disk diffusion method. The BG modification using metal oxides results to antibacterial property of samples containing metal oxide with highest efficiency for nancomposite. bioactivity of all samples was assessed by determining the surface morphology, structural and composition changes using scanning electron microscopy (SEM), FTIR and X-ray diffraction (XRD) spectroscopy, respectively, after soaking in simulated body fluid (SBF) for 28 days. The hydroxyapatite formation was clearly observed as a bioactivity measurement. Then, BG nanocomposite sample was loaded using two antibiotics, separately and their release profiles were studied. The BG nancomposite sample was shown the slow and continuous drug releasing for a period of 72 hours which is desirable for a drug delivery system. The loaded antibiotic nanocomposite sample retaining antibacterial property and showing inactivation effect against bacteria under test. The modified bioactive glass forming hydroxyapatite with controlled release drug and effective against bacterial infections can be introduced as scaffolds for bone implants after clinical trials for biomedical applications . Considering the formation of biofilm by infectious bacteria after sticking on the surfaces of implants, medical devices, etc. Also, considering the complications of traditional methods, solving the problems caused by the above-mentioned microorganisms in technical and biomedical industries was one of the necessities of this research.

Keywords: antibacterial, bioglass, drug delivery system, sol- gel

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Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

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Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

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Authors: Paresh M. Patel, Amit A. Patel, R. H. Parikh

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The present investigation was undertaken to fabricate modified transport fluconazole that belongs to BCS class II and have a poor applicability on topical infection. So to improve topical application, transdermal spray could play a vital role by using ethyl cellulose and Eudragit® S100 as film-forming polymers. Concentration of Eudragit® S100, ethyl cellulose and permeation enhancer (camphor and menthol) were selected as independent variables, whereas drying time, viscosity and in-vitro drug release were selected as dependent variables in factorial design. The viscosity, drying time and in-vitro drug release of the optimize batch B15 was 40.1 cps, 47 sec. and 90.79% respectively. The film of optimized batch was flexible and dermal-adhesive.

Keywords: Eudragit, ethyl cellulose, fluconazole, transdermal spray

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Swapnila V. Shinde, Hemant P. Joshi, Sumit R. Dhas, Dhananjaysingh B. Rajput

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The objective of the present study is to develop hydro-dynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus, site specific oral controlled release floating drug delivery system was developed. Formulation includes novice use of rate controlling polymer such as locust bean gum (LBG) in combination of HPMC K4M and gas generating agent sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables, namely amount of HPMC K4M, LBG and three dependent responses such as cumulative drug release, floating lag time, floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastro-retentive formulation, in vivo gamma scintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of atenolol with improved bioavailability.

Keywords: floating tablet, factorial design, gamma scintigraphy, antihypertensive model drug, HPMC, locust bean gum

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Authors: Parisa Shirzadeh

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Drug delivery systems in which drugs are traditionally used, multi-stage and at specified intervals by patients, do not meet the needs of the world's up-to-date drug delivery. In today's world, we are dealing with a huge number of recombinant peptide and protean drugs and analogues of hormones in the body, most of which are made with genetic engineering techniques. Most of these drugs are used to treat critical diseases such as cancer. Due to the limitations of the traditional method, researchers sought to find ways to solve the problems of the traditional method to a large extent. Following these efforts, controlled drug release systems were introduced, which have many advantages. Using controlled release of the drug in the body, the concentration of the drug is kept at a certain level, and in a short time, it is done at a higher rate. Graphene is a natural material that is biodegradable, non-toxic, and natural compared to carbon nanotubes; its price is lower than carbon nanotubes and is cost-effective for industrialization. On the other hand, the presence of highly effective surfaces and wide surfaces of graphene plates makes it more effective to modify graphene than carbon nanotubes. Graphene oxide is often synthesized using concentrated oxidizers such as sulfuric acid, nitric acid, and potassium permanganate based on Hummer 1 method. In comparison with the initial graphene, the resulting graphene oxide is heavier and has carboxyl, hydroxyl, and epoxy groups. Therefore, graphene oxide is very hydrophilic and easily dissolves in water and creates a stable solution. On the other hand, because the hydroxyl, carboxyl, and epoxy groups created on the surface are highly reactive, they have the ability to work with other functional groups such as amines, esters, polymers, etc. Connect and bring new features to the surface of graphene. In fact, it can be concluded that the creation of hydroxyl groups, Carboxyl, and epoxy and in fact graphene oxidation is the first step and step in creating other functional groups on the surface of graphene. Chitosan is a natural polymer and does not cause toxicity in the body. Due to its chemical structure and having OH and NH groups, it is suitable for binding to graphene oxide and increasing its solubility in aqueous solutions. Graphene oxide (GO) has been modified by chitosan (CS) covalently, developed for control release of doxorubicin (DOX). In this study, GO is produced by the hummer method under acidic conditions. Then, it is chlorinated by oxalyl chloride to increase its reactivity against amine. After that, in the presence of chitosan, the amino reaction was performed to form amide transplantation, and the doxorubicin was connected to the carrier surface by π-π interaction in buffer phosphate. GO, GO-CS, and GO-CS-DOX characterized by FT-IR, RAMAN, TGA, and SEM. The ability to load and release is determined by UV-Visible spectroscopy. The loading result showed a high capacity of DOX absorption (99%) and pH dependence identified as a result of DOX release from GO-CS nanosheet at pH 5.3 and 7.4, which show a fast release rate in acidic conditions.

Keywords: graphene oxide, chitosan, nanosheet, controlled drug release, doxorubicin

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Authors: Bryan Jefry Sabillon, Arlex Molina Cedillo

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Currently, the raise in the demand of electrical energy as a consequence of the development of technology and population growth, as well as some projections made by ‘La Agencia Internacional de la Energía’ (AIE) and research institutes, reveal alarming data about the expected raise of it in the next few decades. Because of this, something should be made to raise the awareness of the rational and efficient usage of this resource. Because of the global concern of providing electrical energy to isolated areas, projects consisting of energy generation using renewable resources are commonly carried out. On a socioeconomically and cultural point of view, it can be foreseen a positive impact that would result for the society to have this resource. This article is focused on the great potential that Honduras shows, as a country that is looking forward to produce renewable energy due to the crisis that it’s living nowadays. Because of this, we present a detailed research that exhibits the main necessities that the rural communities are facing today, to allay the negative aspects due to the scarcity of electrical energy. We also discuss which should be the type of electrical generation method to be used, according to the disposition, geography, climate, and of course the accessibility of each area. Honduras is actually in the process of developing new methods for the generation of energy; therefore, it is of our concern to talk about renewable energy, the exploitation of which is a global trend. Right now the countries’ main energetic generation methods are: hydrological, thermic, wind, biomass and photovoltaic (this is one of the main sources of clean electrical generation). The use of these resources was possible partially due to the studies made by the organizations that focus on electrical energy and its demand, such as ‘La Cooperación Alemana’ (GIZ), ‘La Secretaria de Energía y Recursos Naturales’ (SERNA), and ‘El Banco Centroamericano de Integración Económica’ (BCIE), which eased the complete guide that is to be used in the protocol to be followed to carry out the three stages of this type of projects: 1) Licences and Permitions, 2) Fincancial Aspects and 3) The inscription for the Protocol in Kyoto. This article pretends to take the reader through the necessary information (according to the difficult accessibility that each zone might present), about the best option of electrical generation in zones that are totally isolated from the net, pretending to use renewable resources to generate electrical energy. We finally conclude that the usage of hybrid systems of generation of energy for small remote communities brings about a positive impact, not only because of the fact of providing electrical energy but also because of the improvements in education, health, sustainable agriculture and livestock, and of course the advances in the generation of energy which is the main concern of this whole article.

Keywords: energy, isolated, renewable, accessibility

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Authors: Hind Bouami, Patrick Millot

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Medication dispensing system is a life-critical system whose failure may result in preventable adverse events leading to longer patient stays in hospitals or patient death. Automation has led to great improvements in life-critical systems as it increased safety, efficiency, and comfort. However, critical risks related to medical organization complexity and automated solutions integration can threaten drug dispensing security and performance. Knowledge about the system’s complexity aspects and human machine parameters to control for automated equipment’s security and performance will help operators to secure their automation process and to optimize their system’s reliability. In this context, this study aims to document the operator’s situation awareness about automation risks and parameters involved in automation security and performance. Our risk management approach has been deployed in the North Luxembourg hospital center’s pharmacy, which is equipped with automated drug dispensing systems since 2009. With more than 4 million euros of gains generated, North Luxembourg hospital center’s success story was enabled by the management commitment, pharmacy’s involvement in the implementation and improvement of the automation project, and the close collaboration between the pharmacy and Sinteco’s firm to implement the necessary innovation and organizational actions for automated solutions integration security and performance. An analysis of the actions implemented by the hospital and the parameters involved in automated equipment’s integration security and performance has been made. The parameters to control for automated equipment’s integration security and performance are human aspects (6.25%), technical aspects (50%), and human-machine interaction (43.75%). The implementation of an anthropocentric analysis system before automation would have prevented and optimized the control of risks related to automation.

Keywords: Automated drug delivery systems, Hospitals, Human-centered automated system, Risk management

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Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

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Authors: Osama K. Abou-Zied, Saba A. Sulaiman

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We studied the spectroscopy of 25-nm diameter gold nanoparticles (AuNPs), coated with human serum albumin (HSA) as a model drug carrier. The morphology and coating of the AuNPs were examined using transmission electron microscopy and dynamic light scattering. Resonance energy transfer from the sole tryptophan of HSA (Trp214) to the AuNPs was observed in which the fluorescence quenching of Trp214 is dominated by a static mechanism. Using fluorescein (FL) to probe the warfarin drug-binding site in HSA revealed the unchanged nature of the binding cavity on the surface of the AuNPs, indicating the stability of the protein structure on the metal surface. The transient absorption results of the surface plasmonic resonance (SPR) band of the AuNPs show three ultrafast dynamics that are involved in the relaxation process after excitation at 460 nm. The three decay components were assigned to the electron-electron (~ 400 fs), electron-phonon (~ 2.0 ps) and phonon-phonon (200–250 ps) interactions. These dynamics were not changed upon coating the AuNPs with HSA which indicates the chemical and physical stability of the AuNPs upon bioconjugation. Binding of FL in HSA did not have any measurable effect on the bleach recovery dynamics of the SPR band, although both FL and AuNPs were excited at 460 nm. The current study is important for a better understanding of the physical and dynamical properties of protein-coated metal nanoparticles which are expected to help in optimizing their properties for critical applications in nanomedicine.

Keywords: gold nanoparticles, human serum albumin, fluorescein, femtosecond transient absorption

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Authors: S. S. Pati, L. Herojit Singh, A. C. Oliveira, V. K. Garg

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Chitosan functionalized Fe3O4-Au core shell nanoparticles have been prepared using a two step wet chemical approach using NaBH4 as reducing agent for formation of Au inethylene glycol. X-ray diffraction studies shows individual phases of Fe3O4 and Au in the as prepared samples with crystallite size of 5.9 and 11.4 nm respectively. The functionalization of the core-shell nanostructure with Chitosan has been confirmed using Fourier transform infrared spectroscopy along with signatures of octahedral and tetrahedral sites of Fe3O4 below 600cm-1. Mössbauer spectroscopy shows decrease in particle-particle interaction in presence of Au shell (72% sextet) than pure oleic coated Fe3O4 nanoparticles (88% sextet) at room temperature. At 80K, oleic acid coated Fe3O4 shows only sextets whereas the Chitosan functionalized Fe3O4 and Chitosan functionalized Fe3O4@Au core shell show presence of 5 and 11% doublet, respectively.

Keywords: core shell, drug delivery, gold nanoparticles, magnetic nanoparticles

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Authors: Wadha Alqahtani

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In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

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Authors: Selina Schwaabe

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Community pharmacies deliver high-quality health care and are responsible for medication safety. During the pandemic, accessibility to the nearest pharmacy became more essential to get vaccinated against Covid-19 and to get medical aid. The government's goal is to ensure nationwide, reachable, and affordable medical health care services by pharmacies. Therefore, the density of community pharmacies matters. Overall, the density of community pharmacies is fluctuating, with slightly decreasing tendencies in some countries. So far, the literature has shown that changes in the system affect prices and density. However, a European overview of the development of the density of community pharmacies and its triggers is still missing. This research is essential to counteract against decreasing density consulting in a lack of professional health care through pharmacies. The analysis focuses on liberal versus regulated market structures, mail-order prescription drug regulation, and third-party ownership consequences. In a panel analysis, the relative influence of the measures is examined across 27 European countries over the last 21 years. In addition, the paper examines seven selected countries in depth, selected for the substantial variance in their pharmacy system: Germany, Austria, Portugal, Denmark, Sweden, Finland and Poland. Overall, the results show that regulated pharmacy markets have over 10.75 pharmacies/100.000 inhabitants more than liberal markets. Further, mail-order prescription drugs decrease the density by -17.98 pharmacies/100.000 inhabitants. Countries allowing third-party ownership have 7.67 pharmacies/100.000 inhabitants more. The results are statistically significant at a 0.001 level. The output of this analysis recommends regulated pharmacy markets, with a ban on mail-order prescription drugs allowing third-party ownership to support nationwide medical health care through community pharmacies.

Keywords: community pharmacy, market conditions, pharmacy, pharmacy market, pharmacy lobby, prescription, e-prescription, ownership structures

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Authors: Satya Eswari Jujjavarapu, Swast Dhagat

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Contagious diseases enact severe public health problems and have upsetting consequences. The cyclic lipopeptides explained by bacteria Bacillus, Paenibacillus, Pseudomonas, Streptomyces, Serratia, Propionibacterium and fungus Fusarium are very critical in confining the pathogens. As the degree of drug resistance upsurges in unparalleled manner, the perseverance of searching novel cyclic lipopeptides is being professed. The intense study has shown the implication of these bioactive compounds extending beyond antibacterial and antifungal. Lipopeptides, composed of single units of peptide and fatty acyl moiety, show broad spectrum antimicrobial effects. Among the surplus of cyclic lipopeptides, only few have materialized as strong antibiotics. For their functional vigor, polymyxin, daptomycin, surfactin, iturin and bacillomycin have been integrated in mainstream healthcare. In our work daptomycin has been a major part of antimicrobial resource since the past decade. Daptomycin, a cyclic lipopeptide consists of 13-member amino acid with a decanoyl side-chain. This structure of daptomycin confers it the mechanism of action through which it forms pore in the bacterial cell membrane resulting in the death of cell. Daptomycin is produced by Streptococccus roseoporus and acts against Streptococcus pneumonia (PSRP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The PDB structure and ligands of daptomycin are available online. The molecular docking studies of these ligands with the lipopeptides were performed and their docking score and glide energy were recorded.

Keywords: daptomycin, molecular docking, structure-based drug design, lipopeptide

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Authors: Shamill Amedot Udonwa, Phyllis S. Y. Chong, Lim S. L. Julia, Wee-Joo Chng

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In this paper, we investigated how PRL-3 expression in H929 and U266 cells affects the efficacy of drug treatment. H929 and U266 cells were treated with Bortezomib (BTZ) of different concentrations, and it was observed that H929 cells were resistant to BTZ, while U266 cells were not viable. Investigations into how BTZ targets these cells were conducted, and it was observed that BTZ affects the PARP-Caspase3 pathway as well as PRL-3-Leo1 pathways. These pathways regulate cell proliferation and cell cycle, respectively. Hence, we are able to show the mechanism of how BTZ affects cells and also the role PRL-3 plays on downstream oncogenes such as cyclin-D1 and c-MYC. More importantly, this investigation into PRL-3 in BTZ resistance will be highly applicable in the future as the first clinical trials of PRL-3 antibody (PRL3-zumab) are ongoing at the National University Hospital, Singapore (NUHS). This would mean that understanding the mechanism of resistance through PRL-3, which has yet to be studied, will demonstrate the potential of PRL-3 in developing novel strategies to improve the treatment of MM.

Keywords: drug resistance, hematology, multiple myeloma, oncogene

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Authors: Louise Penzenstadler, Tiphaine Robet, Radu Iuga, Daniele Zullino

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Context: The outpatient clinic of the psychiatric addiction service of Geneva University Hospital has been providing support to individuals affected by various narcotics for 30 years. However, the increasing consumption of crack cocaine in Geneva has presented a new challenge for the healthcare system. Research Aim: The aim of this research is to evaluate the impact of an outreach intervention on crack cocaine addiction in users with co-occurring opioid use disorder. Methodology: The research utilizes a combination of quantitative and qualitative retrospective data analysis to evaluate the effectiveness of the outreach intervention. Findings: The data collected from October 2023 to December 2023 show that the outreach program successfully made 1,071 contacts with drug users and led to 15 new requests for care and enrollment in treatment. Patients expressed high satisfaction with the intervention, citing easy and rapid access to treatment and social support. Theoretical Importance: This research contributes to the understanding of the challenges and specific needs of a complex group of drug users who face severe health problems. It highlights the importance of outreach interventions in establishing trust, connecting users with care, and facilitating medication-assisted treatment for opioid addiction. Data Collection: Data was collected through the outreach program's interactions with drug users, including street outreach interventions and presence at locations frequented by users. Patient satisfaction surveys were also utilized. Analysis Procedures: The collected data was analyzed using both quantitative and qualitative methods. The quantitative analysis involved examining the number of contacts made, new requests for care, and treatment enrollment. The qualitative analysis focused on patient satisfaction and their perceptions of the intervention. Questions Addressed: The research addresses the following questions: What is the impact of an outreach intervention on crack cocaine addiction in users with co-occurring opioid use disorder? How effective is the outreach program in connecting drug users with care and initiating medication-assisted treatment? Conclusion: The outreach program has proven to be an effective intervention in establishing trust with crack users, connecting them with care, and initiating medication-assisted treatment for opioid addiction. It has also highlighted the importance of addressing the specific challenges faced by this group of drug users.

Keywords: crack addiction, outreach treatment, peer intervention, polydrug use

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Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Erin Curtis, Avraham Schwiger

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Neuropsychological testing and evaluation is a crucial step in providing patients with effective diagnoses and treatment while in clinical care. The variety of batteries used in these evaluations can help clinicians better understand the nuanced declivities in a patient’s cognitive, behavioral, or emotional functioning, consequently equipping clinicians with the insights to make intentional choices about a patient’s care. Despite the knowledge these batteries can yield, some aspects of neuropsychological testing remain largely inaccessible to certain patient groups as a result of fundamental cultural, educational, or social differences. One such battery includes the Dot Counting Test (DCT), during which patients are required to count a series of dots on a page as rapidly and accurately as possible. As the battery progresses, the dots appear in clusters that are designed to be easily multiplied. This task evaluates a patient’s cognitive functioning, attention, and level of effort exerted on the evaluation as a whole. However, there is evidence to suggest that certain social groups, particularly Latinx groups, may perform worse on this task as a result of cultural or educational differences, not reduced cognitive functioning or effort. As such, this battery fails to account for baseline differences among patient groups, thus creating questions surrounding the accuracy, generalizability, and value of its results. Accessibility and cultural sensitivity are critical considerations in the testing and treatment of marginalized groups, yet have been largely ignored in the literature and in clinical settings to date. Implications and improvements to applications are discussed.

Keywords: culture, latino, neuropsychological assessment, neuropsychology, accessibility

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Authors: Anurag Gaur Nidhi

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Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. This improves efficacy of the while reducing side effects. In the present work, we investigate the effect of magnetic field, flow rate and particle concentration on the capturing of magnetic particles transported in a stent implanted fluidic channel. Iron oxide magnetic nanoparticles (Fe3O4) nanoparticles were synthesized via co-precipitation method. The synthesized Fe3O4 nanoparticles were added in the de-ionized (DI) water to prepare the Fe3O4 magnetic particle suspended fluid. This fluid is transported in a cylindrical tube of diameter 8 mm with help of a peristaltic pump at different flow rate (25-40 ml/min). A ferromagnetic coil of SS 430 has been implanted inside the cylindrical tube to enhance the capturing of magnetic nanoparticles under magnetic field. The capturing of magnetic nanoparticles was observed at different magnetic magnetic field, flow rate and particle concentration. It is observed that capture efficiency increases from 47-67 % at magnetic field 2-5kG, respectively at particle concentration 0.6 mg/ml and at flow rate 30 ml/min. However, the capture efficiency decreases from 65 to 44 % by increasing the flow rate from 25 to 40 ml/min, respectively. Furthermore, it is observed that capture efficiency increases from 51 to 67 % by increasing the particle concentration from 0.3 to 0.6 mg/ml, respectively.

Keywords: capture efficiency, implant assisted-Magnetic drug targeting (IA-MDT), magnetic nanoparticles, In-vitro study

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Authors: Yassir Adam Shuaib, Stefan Niemann, Eltahir Awad Khalil, Ulrich Schaible, Lothar Heinz Wieler, Mohammed Ahmed Bakhiet, Abbashar Osman Mohammed, Mohamed Abdelsalam Abdalla, Elvira Richter

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Tuberculosis (TB) is a chronic bacterial disease of humans and animals and it is characterized by the progressive development of specific granulomatous tubercle lesions in affected tissues. In a six-month study, from June to November 2014, a total of 2,304 carcasses of cattle, camel, sheep, and goats slaughtered at East and West Gaash slaughterhouses, Kassala, were investigated during postmortem, in parallel, 101 sputum samples from TB suspected patients at Kassala and El-Gadarif Teaching Hospitals were collected in order to investigate tuberculosis in animals and humans. Only 0.1% carcasses were found with suspected TB lesions in the liver and lung and peritoneal cavity of two sheep and no tuberculous lesions were found in the carcasses of cattle, goats or camels. All samples, tissue lesions and sputum, were decontaminated by the NALC-NaOH method and cultured for mycobacterial growth at the NRZ for Mycobacteria, Research Center Borstel, Germany. Genotyping and molecular characterization of the grown strains were done by line probe assay (GenoType CM and MTBC) and 16S rDNA, rpoB gene, and ITS sequencing, spoligotyping, MIRU-VNTR typing and next generation sequencing (NGS). Culture of the specimens revealed growth of organisms from 81.6% of all samples. Mycobacterium tuberculosis (76.2%), M. intracellulare (14.2%), mixed infection with M. tuberculosis and M. intracellulare (6.0%) and mixed infection with M. tuberculosis and M. fortuitum and with M. intracellulare and unknown species (1.2%) were detected in the sputum samples and unknown species (1.2%) were detected in the samples of one of the animals tissues. From the 69 M. tuberculosis strains, 25 (36.2%) were showing either mono-drug-resistant or multi-drug-resistant or poly-drug-resistant but none was extensively drug-resistant. In conclusion, the prevalence of TB in animals was very low while in humans M. tuberculosis-Delhi/CAS lineage was responsible for most cases and there was an evidence of MDR transmission and acquisition.

Keywords: animal, human, slaughterhouse, Sudan, tuberculosis

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Authors: Hoda Sabry Othman, Randa Helmy Swellem, Galal Abd El-Moein Nawwar

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N-cyanoacetyl glycine is a reactive polyfunctional precursor for synthesis of new difficult accessible compounds including pyridones, thiazolopyridine and others. The key step of this protocol is the formation of different ylidines which underwent Michael addition with carbon nucleophiles affording various heterocyclic compounds. Selected compounds underwent pharmacological evaluation, in vitro against two cell lines; breast cell line (MCF-7),and liver cell line(HEPG2). Compounds 14, 15a and 16 showed IC50 values 8.93, 8.18 and 8.03 (µ/ml) respectively for breast cell line (MCF-7), while the standard drug (Tamoxifen) revealed IC50 8.31. With respect to the liver cell line (HEPG2), compounds 14 and 15a revealed IC50 18.4 and 13.6(µ/ml) respectively while the IC50 of the standard drug(5-Flurouracil) is 25(µ/ml). The antimicrobial activity was also screened and revealed that oxime 7 and ylidine 9f showed a broad-spectrum activity.

Keywords: antitumor, cyanoacetyl glycine, heterocycles, pyridones

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Authors: Florin G. Borcan, Ramona C. Albulescu, Adela Chirita-Emandi

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pH-responsive drug delivery systems are gaining more importance because these systems deliver the drug at a specific time in regards to pathophysiological necessity, resulting in improved patient therapeutic efficacy and compliance. Polyurethane materials are well-known for industrial applications (elastomers and foams used in different insulations and automotive), but they are versatile biocompatible materials with many applications in medicine, as artificial skin for the premature neonate, membrane in the hybrid artificial pancreas, prosthetic heart valves, etc. This study aimed to obtain the physico-chemical characterization of a drug delivery system based on polyurethane microparticles. The synthesis is based on a polyaddition reaction between an aqueous phase (mixture of polyethylene-glycol M=200, 1,4-butanediol and Tween® 20) and an organic phase (lysin-diisocyanate in acetone) combined with simultaneous emulsification. Different active agents (omeprazole, amoxicillin, metoclopramide) were used to verify the release profile of the macromolecular particles in different pH mediums. Zetasizer measurements were performed using an instrument based on two modules: a Vasco size analyzer and a Wallis Zeta potential analyzer (Cordouan Technol., France) in samples that were kept in various solutions with different pH and the maximum absorbance in UV-Vis spectra were collected on a UVi Line 9,400 Spectrophotometer (SI Analytics, Germany). The results of this investigation have revealed that these particles are proper for a prolonged release in gastric medium where they can assure an almost constant concentration of the active agents for 1-2 weeks, while they can be disassembled faster in a medium with neutral pHs, such as the intestinal fluid.

Keywords: lysin-diisocyanate, nanostructures, polyurethane, Zetasizer

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Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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Authors: Amel Chenafa, Sihem Boulenouar, Linda Aoued, Imane Sediri, Ismahan Djebbar, Mohamed Adil Selka

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Introduction: The specialties intended for adults are often inadequate marketed for pediatric use, such as for a galenic form or in the dosage. For an industrial, development of a pediatric drug is confronted to various problems. So, the hospital pharmacies have to respond to adaptation needs of pharmaceutical forms for pediatric use. The objective of our work is to develop an oral form of prednisone for pediatric use since no adapted form to children is commercialized. Materials and Methods: Therefore an extemporaneous syrup of prednisone was prepared at the concentration of 0,5mg/ml from 5mg tablets and stored in amber glass bottles. Organoleptic and microbiological stability was studied in two temperatures: 5°C and 25°C, and evaluated at D0, D15, and D30. Results: No organoleptic changes have been detected on the syrup conserved at 25 and 5°C. The results show that there is no presence of bacteria, yeasts, and molds in the syrups stored at both temperatures during the analysis period. Conclusion: Sheltered from light, the developed syrup of prednisone remained stable at room temperature and/or refrigerator for 30 days.

Keywords: extemporaneous syrup, pediatric drug, prednisone, stability

Procedia PDF Downloads 386

Authors: Patricia Huedo, Maria José Ruá, Raquel Agost-Felip

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Ensuring sustainable development of urban environments means guaranteeing adequate environmental conditions, being resilient and meeting conditions of safety and inclusion for all people, regardless of their condition. All existing buildings should meet basic safety conditions and be equipped with safe and accessible routes, along with visual, acoustic and tactile signals to protect their users or potential visitors, and regardless of whether they undergo rehabilitation or change of use processes. Moreover, from a social perspective, we consider the need to prioritize buildings occupied by the most vulnerable groups of people that currently do not have specific regulations tailored to their needs. Some residential models in operation are not only outside the scope of application of the regulations in force; they also lack a project or technical data that would allow knowing the fire behavior of the construction materials. However, the difficulty and cost involved in adapting the entire building stock to current regulations can never justify the lack of safety for people. Hence, this work develops a simplified model to assess compliance with the basic safety conditions in case of fire and its compatibility with the specific accessibility needs of each user. The purpose is to support the designer in decision making, as well as to contribute to the development of a basic fire safety certification tool to be applied in inclusive residential models. This work has developed a methodology to support designers in adapting Social Services Centers, usually intended to vulnerable people. It incorporates a checklist of 9 items and information from sources or standards that designers can use to justify compliance or propose solutions. For each item, the verification system is justified, and possible sources of consultation are provided, considering the possibility of lacking technical documentation of construction systems or building materials. The procedure is based on diagnosing the degree of compliance with fire conditions of residential models used by vulnerable groups, considering the special accessibility conditions required by each user group. Through visual inspection and site surveying, the verification model can serve as a support tool, significantly streamlining the diagnostic phase and reducing the number of tests to be requested by over 75%. This speeds up and simplifies the diagnostic phase. To illustrate the methodology, two different buildings in the Valencian Region (Spain) have been selected. One case study is a mental health facility for residential purposes, located in a rural area, on the outskirts of a small town; the other one, is a day care facility for individuals with intellectual disabilities, located in a medium-sized city. The comparison between the case studies allow to validate the model in distinct conditions. Verifying compliance with a basic security level can allow a quality seal and a public register of buildings adapted to fire regulations to be established, similarly to what is being done with other types of attributes such as energy performance.

Keywords: fire safety, inclusive housing, universal accessibility, vulnerable people

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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Authors: Dau Lal Bohra, Sradha Vyas

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Bird species are already showing climate-related changes in the dates they migrate and breed, and in the timing of other key life-history events. Treats of feeding managements raptors have performed important ecological, traditional and aesthetic functions throughout the Indian subcontinent. The declines in India result from elevated adult and juvenile mortality, and low breeding success. The widespread and rapid pattern of declines, i.e. in all areas irrespective of habitat or protection status suggest that persecution through shooting or poisoning, whilst important at a local scale, are unlikely to have caused the declines. A mass killing of several species of vultures in the Indian subcontinent over the last two decades is largely blamed on the presence of a drug. Veterinary diclofenac caused an unprecedented decline in South Asia’s Gyps vulture populations, with some species declining by more than 97% between 1992 and 2007. Veterinary diclofenac causes renal failure in vultures, and killed tens of millions of such birds in the Indian sub-continent. The drug was finally banned there for veterinary purposes in 2006. This drug is now ‘a global problem’ threatening many vulnerable birds of prey. Recently, stappe eagles are also susceptible to veterinary diclofenac, effectively increasing the potential threat level, and the risks for European biodiversity. Steppe eagles are closely related with golden eagles (Aquila chrysaetus), imperial eagles (Aquila heliaca) and Spanish imperial eagles (Aquila adalberti), and all these species scavenge opportunistically on carcasses throughout their range. The Spanish imperial eagle, considered Vulnerable at global level, is now particularly at risk, due to the availability of diclofenac in Spain. These findings strengthen the case for banning veterinary diclofenac across. From year 2011 to 2014 more than 300 hundred birds dead in jorbeer, Bikaner. Now, with unequivocal evidence that this veterinary drug can cause a much wider impact on Europe´s biodiversity, it is time for action – please ban diclofenac human brand also in multi-dose vial from market.

Keywords: mortility, prey of birds, diclofenac, Rajasthan

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Authors: Abdulwahhab Khedr, Tamer Shehata, Hanaa El-Ghamry

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Venlafaxine HCl is a novel antidepressant drug used in the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder. Conventional therapeutic regimens with venlafaxine HCl immediate-release dosage forms require frequent dosing due to short elimination half-life of the drug and reduced bioavailability. Hence, this study was carried out to develop sustained-release dosage forms of venlafaxine HCl to reduce its dosing frequency, to improve patient compliance and to reduce side effects of the drug. The polymers used were hydroxypropylmethyl cellulose, xanthan gum, sodium alginate, sodium carboxymethyl cellulose, Carbopol 940 and ethyl cellulose. The physical properties of the prepared tablets including tablet thickness, diameter, weight uniformity, content uniformity, hardness and friability were evaluated. Also, the in-vitro release of venlafaxine HCl from different matrix tablets was studied. Based on physical characters and in-vitro release profiles, certain formulae showing promising sustained-release profiles were subjected to film coating with 15% w/v EC in dichloromethane/ethanol mixture (1:1 ratio) using 1% w/v HPMC as pore former and 30% w/w dibutyl phthalate as plasticizer. The optimized formulations were investigated for drug-excipient compatibility using FTIR and DSC studies. Physical evaluation of the prepared tablets fulfilled the pharmacopoeial requirements for tablet friability test, where the weight loss of the prepared formulae did not exceed 1% of the weight of the tested tablets. Moderate release was obtained from tablets containing HPMC. FTIR and DSC studies for such formulae revealed the absence of any type of chemical interaction between venlafaxine HCl and the used polymers or excipients. Forced swimming test in rats was used to evaluate the antidepressant activity of the selected matrix tablets of venlafaxine HCl. Results showed that formulations significantly decreased the duration of animals’ immobility during the 24 hr-period of the test compared to non-treated group.

Keywords: antidepressant, sustained-release, matrix tablet, venlafaxine hydrochloride

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Authors: Simone Galati, Adriano Troia

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Ultrasound (US) is widely used in medical field for a variety diagnostic techniques but, in recent years, it has also been creating great interest for therapeutic aims. Regarding drug delivery, the use of US as an activation source provides better spatial delivery confinement and limits the undesired side effects. However, at present there is no complete characterization at a fundamental level of the different signals produced by sono-activated nanocarriers. Therefore, the aim of this study is to obtain a metrological characterization of the cavitation phenomena induced by US through three parallel investigation approaches. US was focused into a channel of a customized phantom in which a solution with oxygen-loaded nanodroplets (OLNDs) was led to flow and the cavitation activity was monitored. Both quantitative and qualitative real-time analysis were performed giving information about the dynamics of bubble formation, oscillation and final implosion with respect to the working acoustic pressure and the type of nanodroplets, compared with pure water. From this analysis a possible interpretation of the observed results is proposed.

Keywords: cavitation, drug delivery, nanodroplets, ultra-sound

Procedia PDF Downloads 111