Search results for: drug combinations

Authors: Sarah Nasr, Maha M. A. Nasra, Ossama Y. Abdallah

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The present work aimed to prepare Silymarin loaded MCM-41 type mesoporous silica nanoparticles (MSNs) and to assess the system’s solubility enhancement ability on the pharmacodynamic performance of Silymarin as a hepatoprotective agent. MSNs prepared by soft-templating technique, were loaded with Silymarin, characterized for particle size, zeta potential, surface properties, DSC and XRPD. DSC and specific surface area data confirmed deposition of Silymarin in an amorphous state in MSNs’ pores. In-vitro drug dissolution testing displayed enhanced dissolution rate of Silymarin upon loading on MSNs. High dose Acetaminophen was then used to inflict hepatic injury upon albino male Wistar rats simultaneously receiving either free Silymarin, Silymarin loaded MSNs or blank MSNs. Plasma AST, ALT, albumin and total protein and liver homogenate content of TBARs or LDH as measures of antioxidant drug action were assessed for all animal groups. Results showed a significant superiority of Silymarin loaded MSNs to free drug in almost all parameters. Meanwhile prolonged administration of blank MSNs had no evident toxicity on rats.

Keywords: mesoporous silica nanoparticles, safety, solubility enhancement, silymarin

Procedia PDF Downloads 310

Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

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Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

Procedia PDF Downloads 153

Authors: Saeed Abbasi, Davood Farsi, Soudabeh Shafiee Ardestani, Neda Valizadeh

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Objectives: Peripheral vertigo is a common complaint of patients who are visited in emergency departments. In our study, we wanted to evaluate the effect of betahistine as an oral drug vs. intravenous diazepam for the treatment of acute peripheral vertigo. We also wanted to see the possibility of substitution of parenteral drug with an oral one with fewer side effects. Materials and Methods: In this randomized, double-blind study, 101 patients were enrolled in the study. The patients were divided in two groups in a double-blind randomized manner. Group A took oral placebo and 10 mg of intravenous diazepam. Group B received 8mg of oral betahistine and intravenous placebo. Patients’ symptoms and signs (Vertigo severity, Nausea, Vomiting, Nistagmus and Gate) were evaluated after 0, 2, 4, 6 hours by emergency physicians and data were collected by a questionnaire. Results: In both groups, there was significant improvement in vertigo (betahistine group P=0.02 and Diazepam group P=0.03). Analysis showed more improvement in vertigo severity after 4 hours of treatment in betahistine group comparing to diazepam group (P=0.02). Nausea and vomiting were significantly lower in patients receiving diazepam after 2 and 6 hours (P=0.02 & P=0.03).No statistically significant differences were found between the groups in nistagmus, equilibrium & vertigo duration. Conclusion: The results of this randomized trial showed that both drugs had acceptable therapeutic effects in peripheral vertigo, although betahistine was significantly more efficacious after 4 hours of drug intake. As for higher nausea and vomiting in betahistine group, physician should consider these side effects before drug prescription.

Keywords: acute peripheral vertigo, betahistine, diazepam, emergency department

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Authors: Ahmad Shah Farhat, Anahita Alizadeh Qamsari, Ashraf Mohammadzadeh, Hamid Reza Goldouzian, Ezat Khodashenas

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Introduction: Newborns may be treated with phenobarbital for many reasons. Because in each region, depending on different races and genetic factors, different pharmacokinetic conditions govern the drug. It is essential to control blood levels of certain drugs, especially phenobarbital, and maintain these levels during treatment. Methods: In this study, venous blood was collected from 50 neonates who received intravenous phenobarbital at a loading dose of 20 mg/kg weight and at least three days had passed since the maintenance dose of 5 mg/kg body weight. in 24 hours. and sent to the laboratory. Phenobarbital blood levels were measured, then the results were analyzed descriptively. Results: In this study, the average weight of newborns was 9.93 ± 2.58. The mean blood concentration of phenobarbital, three days after starting the maintenance dose in the group of infants weighing more than 2.5 kg, was 3.33 ± 9.1 micrograms/liter in the group of infants weighing less than 2 kg. and half a kilogram or LBW was 5.9 ± 9.5 micrograms/liter and in the group weighing less than 1.5 kg VLBW was 14.4 ± 15.46 micrograms/liter. There was no significant difference between groups (p>0.05). Three days after starting the maintenance dose in all three groups, the mean blood phenobarbital concentration was 9.86 ± 0.86 micrograms/liter. Conclusion: Blood phenobarbital levels in our newborns are below therapeutic levels, so phenobarbital levels should be evaluated.

Keywords: poisining, neonats, phenobarbital, drug

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Authors: J. P. Lavande, A. V.Chandewar

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Mouth dissolving tablet is the speedily growing and highly accepted drug delivery system. This study was aimed at development of Ketorolac Tromethamine mouth dissolving tablet (MDTs), which can disintegrate or dissolve rapidly once placed in the mouth. Conventional Ketorolac tromethamine tablet requires water to swallow it and has limitation like low disintegration rate, low solubility etc. Ketorolac Tromethamine mouth dissolving tablets (formulation) consist of super-disintegrate like Heat Modified Karaya Gum, Co-treated Heat Modified Agar & Filler microcrystalline cellulose (MCC). The tablets were evaluated for weight variation, friability, hardness, in vitro disintegration time, wetting time, in vitro drug release profile, content uniformity. The obtained results showed that low weight variation, good hardness, acceptable friability, fast wetting time. Tablets in all batches disintegrated within 15-50 sec. The formulation containing superdisintegrants namely heat modified karaya gum and heat modified agar showed better performance in disintegration and drug release profile.

Keywords: mouth dissolving tablet, Ketorolac tromethamine, disintegration time, heat modified karaya gum, co-treated heat modified agar

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Authors: Ponshano Kaselekela, Simooya O. Oscar, Lunshano Boyd

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The Copperbelt University Health Services (CBUHS) was designated by the Zambia Medicines Regulatory Authority (ZAMRA), formally the Pharmaceutical Regulatory Authority (PRA) as a regional pharmacovigilance centre to carryout activities of drug safety monitoring in four provinces in Zambia. CBUHS’s mandate included stimulating the reporting of adverse drug reactions (ADRs), as well as collecting and collating ADR reports from health institutions in the four provinces. This report covers the researchers’ experiences from May 2008 to September, 2016. The main objectives are 1) to monitor ADRs in the Zambian population, 2) to disseminate information to all health professionals in the region advising that the CBU health was a centre for reporting ADRs in the region, 3) to monitor polypharmacy as well as the benefit-risk profile of medicines, 4) to generate independent, evidence based recommendations on the safety of medicines, 5) to support ZAMRA in formulating safety related regulatory decisions for medicines, and 6) to communicate findings with all key stakeholders. The methodology involved monthly visits, beginning in early May 2008 to September, 2016, by the CBUHS to health institutions in the programme areas. Activities included holding discussions with health workers, distribution of ADR forms and collection of ADRs reports. These reports, once collected, were documented and assessed at the CBUHS. A report was then prepared for ZAMRA on quarterly basis. At ZAMRA, serious ADRs were noted and recommendations made to the Ministry of Health of the Republic of Zambia. The results show that 2,600 ADRs reports were received at the pharmacovigilance regional centre. Most of the ADRs reports that received were due to antiretroviral drugs, as well as a few from anti-malarial drugs like Artemether/Lumefantrine – Coartem®. Three hundred and twelve ADRs were entered in the Uppsala Monitoring Centre WHO Vigiflow for further analysis. It was concluded that in general, 2008-16 were exciting years for the pharmacovigilance group at CBUHS. From a very tentative beginning, a lot of strides were made and contacts established with healthcare facilities in the region. The researchers were encouraged by the support received from the Copperbelt University management, the motivation provided by ZAMRA and most importantly the enthusiasm of health workers in all the health care facilities visited. As a centre for drug safety in Zambia, the results show it achieves its objectives for monitoring ADRs, Pharmacovigilance (drug safety monitoring), and activities of monitoring ADRs as well as preventing them. However, the centre faces critical challenges caused by erratic funding that prevents the smooth running of the programme.

Keywords: adverse drug reactions, drug safety, monitoring, pharmacovigilance

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Authors: Sahar Iqrar, Malik Adeel Anwar, Zain Akram, Maria Noor

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Introduction: Oral lichen planus is a chronic inflammatory condition of unknown etiology. Oral lichen planus may be related with several other diseases. Grinspan's Syndrome is characterized by a triad of oral lichen planus, hypertension, and diabetes mellitus. Other associations reported in the literature are with chronic liver disease and, with dyslipidemia. The nature of these associations is still not fully understood. Material and methods: Study was conducted in Department of Oral Medicine, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan. A total of n=89 clinically diagnosed patients of oral lichen planus of both gender and all age groups were recruited and detailed history were recorded in the designed performs. Results: A total of n=89 patients were taken with male to female ratio of 3:8 in which 24 were male and 65 females. Mean age was 48.8 ± 13.8 years. Age range of 10-74 years was seen. Among these patients suffering from oral lichen planus, 41.6% (n=37) had a positive history for hypertension with 59.5% (n=22) of these patients were taking different medication for their condition. Whereas Diabetes Mellitus was found in 24.7% (n=22) patients with 72.7% (n=16) of these patients using the hypoglycemic drug (oral or injectable) to control their blood glucose levels. Out of these n=89 lichen planus patients 21.3% had both hypertension and diabetes mellitus (fulfilling the criteria for Grinspan's Syndrome). Out of this Grinspan's Syndrome pool 94.7% (n=19) were taking drug atleast for one of the two conditions. Conclusion: As noticed form the medical history of the patients, most of them were using hypoglycemic drugs for diabetes mellitus and beta blockers, diuretics and calcium channel blockers for hypertension. These drugs are known for lichenoid reaction. Therefore, it should be ruled out at histopathological/ immunological and molecular level whether these patients are suffering from lichen planus or lichenoid drug reaction to truly declare them as patients with Grinspan’s Syndrome.

Keywords: diabetes mellitus, grinspan's syndrome, lichenoid drug reaction, oral lichen planus

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Authors: Pritika Ramharack, Mahmoud E. S. Soliman

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The re-emerging Zika virus is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus already been linked to irreversible chronic central nervous system (CNS) conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA-approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of Zika virus Methyltransferase and RNA-dependent RNA polymerase. This in silico “per-residue energy decomposition pharmacophore” virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.

Keywords: NS5 protein inhibitors, per-residue decomposition, pharmacophore model, virtual screening, Zika virus

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

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

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

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Authors: Cynthia K. Burzell

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Aequor's Founder, a Marine and Medical Microbiologist, discovered novel, non-toxic chemicals in the ocean that uniquely remove biofilm in minutes and prevent its formation for days. These chemicals and over 70 synthesized analogs that Aequor developed can replace thousands of toxic biocides used in consumer and industrial products and, as new drug candidates, kill biofilm-forming bacteria and fungi Superbugs -the antimicrobial-resistant (AMR) pathogens for which there is no cure. Cynthia Burzell, PhD., is a Marine and Medical Microbiologist studying natural mechanisms that inhibit biofilm formation on surfaces in contact with water. In 2002, she discovered a new genus and several new species of marine microbes that produce small molecules that remove biofilm in minutes and prevent its formation for days. The molecules include new antimicrobials that can replace thousands of toxic biocides used in consumer and industrial products and can be developed into new drug candidates to kill the biofilm-forming bacteria and fungi -- including the antimicrobial-resistant (AMR) Superbugs for which there is no cure. Today, Aequor has over 70 chemicals that are divided into categories: (1) Novel natural chemicals. Lonza validated that the primary natural chemical removed biofilm in minutes and stated: "Nothing else known can do this at non-toxic doses." (2) Specialty chemicals. 25 of these structural analogs are already approved under the U.S. Environmental Protection Agency (EPA)'s Toxic Substances Control Act, certified as "green" and available for immediate sale. These have been validated for the following agro-industrial verticals: (a) Surface cleaners: The U.S. Department of Agriculture validated that low concentrations of Aequor's formulations provide deep cleaning of inert, nano and organic surfaces and materials; (b) Water treatments: NASA validated that one dose of Aequor's treatment in the International Space Station's water reuse/recycling system lasted 15 months without replenishment. DOE validated that our treatments lower energy consumption by over 10% in buildings and industrial processes. Future validations include pilot projects with the EPA to test efficacy in hospital plumbing systems. (c) Algae cultivation and yeast fermentation: The U.S. Department of Energy (DOE) validated that Aequor's treatment boosted biomass of renewable feedstocks by 40% in half the time -- increasing the profitability of biofuels and biobased co-products. DOE also validated increased yields and crop protection of algae under cultivation in open ponds. A private oil and gas company validated decontamination of oilfield water. (3) New structural analogs. These kill Gram-negative and Gram-positive bacteria and fungi alone, in combinations with each other, and in combination with low doses of existing, ineffective antibiotics (including Penicillin), "potentiating" them to kill AMR pathogens at doses too low to trigger resistance. Both the U.S. National Institutes for Health (NIH) and Department of Defense (DOD) has executed contracts with Aequor to provide the pre-clinical trials needed for these new drug candidates to enter the regulatory approval pipelines. Aequor seeks partners/licensees to commercialize its specialty chemicals and support to evaluate the optimal methods to scale-up of several new structural analogs via activity-guided fractionation and/or biosynthesis in order to initiate the NIH and DOD pre-clinical trials.

Keywords: biofilm, potentiation, prevention, removal

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Authors: Oktira Roka Aji, Maelita R. Moeis, Ihsanawati, Ernawati A. Giri-Rachman

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Globally, tuberculosis (TB) remains a leading cause of death. The emergence of multidrug-resistant strains and extensively drug-resistant strains have become a major public concern. One of the potential candidates for drug target is the cytoplasmic domain of PhoR Histidine Kinase, a part of the Two Component System (TCS) PhoR-PhoP in Mycobacterium tuberculosis (Mtb). TCS PhoR-PhoP relay extracellular signal to control the expression of 114 virulent associated genes in Mtb. The 3D structure of PhoR cytoplasmic domain is needed to screen novel drugs using structure based drug discovery. The PhoR cytoplasmic domain from Mtb H37Rv was overexpressed in E. coli BL21(DE3), then purified using IMAC Ni-NTA Agarose his-tag affinity column and DEAE-ion exchange column chromatography. The molecular weight of the purified protein was estimated to be 37 kDa after SDS-PAGE analysis. This sample was used for pre-crystallization screening by applying sitting drop vapor diffusion method using Natrix (HR2-116) 48 solutions crystal screen kit at 25ºC. Needle-like crystals were observed after the seventh day of incubation in test solution No.47 (0.1 M KCl, 0.01 M MgCl2.6H2O, 0.05 M Tris-Cl pH 8.5, 30% v/v PEG 4000). Further testing is required for confirming the crystal.

Keywords: tuberculosis, two component system, histidine kinase, needle-like crystals

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Authors: J. Oustric, L. Berti, J. Santini

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Nowadays, the objective of durable agriculture, and in particular organic agriculture, is to reduce the level of fertilizer inputs used in crops. Limiting the quantity of fertilizer inputs would optimize the economical result and minimizing the environmental impact. Nutrient deficiency, particularly of a major nutrient (N, P, and K), can seriously affect fruit production and quality. In citrus crops, rootstock/scion combinations. In citrus crop, scion/rootstock combinations are used frequently to improve tolerance to various abiotic stresses. New rootstocks are needed to respond to these constraints, and the use of new tetraploid rootstocks better adapted to lower nutrient intake could offer a promising way forward. The aim of this work was to determine whether a better tolerance to nutrient deficiency could be observed in a doubled diploid seedling and whether this tolerance could be observed in common clementine scion if used as rootstocks. We selected diploid (CM2x) and doubled diploid (CM4x) Citrumelo 4475 seedlings and common clementine (C) grafted onto Citrumelo 4475 diploid (C/CM2x) and doubled diploid (C/CM4x) rootstocks. Nutrient deficiency effects on the seedlings and scion/rootstock combinations were analyzed by studying anatomical, structural and ultrastructural determinants (chlorosis, stomata, ostiole and cells and their organelles), photosynthetic properties (leaf net photosynthetic rate (Pₙₑₜ), stomatal conductance (gₛ), chlorophyll a fluorescence (Fᵥ/Fₘ)) and oxidative marker (malondialdehyde). Nutrient deficiency affected differently foliar tissues, physiological parameters, and oxidative metabolism in leaves of seedlings depending on their ploidy level and of common clementine scion depending on their rootstocks ploidy level. Both CM4x and C/CM4x presented lower foliar damages (chlorosis, chloroplasts, mitochondria, and plastoglobuli), photosynthesis processes alteration (Pₙₑₜ, gₛ, and Fᵥ/Fₘ), and malondialdehyde accumulation than CM2x and C/CM2x after nutrient deficiency. Doubled diploid Citrumelo 4475 can improve nutrient deficiency tolerance, and its use as a rootstock allows to confer this tolerance to the common clementine scion.

Keywords: nutrient deficiency, oxidative stress, photosynthesis, polyploid rootstocks

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Authors: Abhay Asthana, Shally Toshkhani, Gyati Shilakari

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

Keywords: wound healing, biodegradable, polymers, patch

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Authors: Zahid Iqbal, Ijaz Javed, Riaz Hussain, Ibadullah Jan, Amir Ali Khan

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This study was conducted to investigate the disposition kinetics of ciprofloxacin and calculate its optimal dosage in Pakistani sheep of Lohi breed. Injectable preparation of ciprofloxacin was given intramuscularly to eight sheep at a dose of 5 mg/Kg. Before administration of drug blood sample was drawn from each animal. Post drug administration, blood samples were also drawn at various predetermined time periods. Drug concentration in the blood samples was assessed through high performance liquid chromatograph (HPLC). Data were best described by two compartment open model and different pharmacokinetic (PK) parameters were calculated. Cmax of 1.97 ± 0.15 µg/ml was reached at Tmax of 0.88 ± 0.09 hours. Half life of absorption (t1/2 abs) was observed to be 0.63 ± 0.16 hours while t1/2 α (distribution half life) and t1/2 ß (elimination half life) were found to be 0.46 ± 0.05 and 2.93 ± 0.45 hours, respectively. Vd (apparent volume of distribution) was calculated as 2.89 ± 0.30 L/kg while AUC (area under the curve) was 7.19 ± 0.38 µg.hr/mL and CL (total body clearance) was 0.75 ± 0.04 L/hr/kg. Using these parameters, an optimal intramuscular dosage of ciprofloxacin in adult Lohi sheep was calculated as 21.43 mg/kg, advised to be repeated after 24 hours. From this, we came to the conclusion that calculated dose was much higher than the dose advised by the foreign manufacturer and to avoid antimicrobial resistance, it is advised that this locally investigated dosage regimen should be strictly followed in local sheep.

Keywords: pharmacokinetics, dosage regimen, ciprofloxacin, HPLC, sheep

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Authors: G. Wagner, R. Herrmann

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Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: cytotoxicity, mesoporous silica, nanoparticles, platinum compounds

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Authors: Sertac Arslan, Guven Guney, Ayse Ipek Akyuz Unsal, Emre Demir, Buket Demirci

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Purpose: There is little histologic data concerning effects of nasal decongestants on the respiratory tract. We aimed to put forth the effects of nasal decongestants on the trachea and lower airways of rats. Materials and Methods: Four to six months old 60 male rats were randomly categorized into 6 groups. Experimental drugs were applied to the same nostril of rats twice daily for 8 weeks (Xylometazolin, Benzalkolyum, EDTA, Sorbitol and combined drug solutions). We applied normal saline solution (NaCl %0.9) for the control group. In the end, trachea and both lungs were dissected and kept in formaldehyde for histopathologic evaluation. Results: Inflammation and bronchial edema were most common findings. While all rats in sorbitol group had increased numbers of type 2 pneumocytes; 80% of BAC group had increased numbers of type 2 pneumocytes. Spillover of tracheal epithelium was seen mostly in sorbitol, EDTA and combined drug groups (60%, 87.5%, 50% respectively). Bronchial smooth muscle hypertrophy was seen mostly in BAC and EDTA group (70%, 62.5% respectively). The number of goblet cells showed the significant difference between control-combined drug (p=0.025) and control-BAC (p=0.001) groups. Conclusions: Nasal decongestants can cause permanent changes at lower respiratory tract in addition to changes in upper respiratory tract.

Keywords: decongestive agents, xylometazoline, lung, trachea

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Authors: Muhammad Mustaqeem, Musa Kaleem Baloch, Irfan Ullah, Ammarah Luqman, Afshan Ahmad

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Flurbiprofen is one of the most potent nonsteroidal anti-inflammatory drugs. It is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrhea. However, its aqueous solubility is very low and hinders the skin permeation. Thus, it is imperative to develop such a drug delivery systems which can improve its aqueous solubility and hence improve the skin permeation and therapeutic compliance. Microemulsions have been also proven to increase the cutaneous absorption of lipophilic drugs as compared to conventional vehicles. Micro-emulsion is thermodynamically stable emulsion that has the capacity to ‘hide/solubilize’ water-insoluble molecules within a continuous oil phase. Therefore, flurbiprofen was converted to Easters through chemical reactions with alcohols such as methanol, ethanol, propanol and butanol. The product was further treated with hydrazine to get hydrazide. The solubility of the parent drug Flurbiprofen and the products were solubilized in microemulsions formed using various surfactants like ionic, non-ionic and zwitterions. It has been concluded that the product was more soluble than the parent compound. The biological activities of these were also investigated. The outcome was very promising and the product was more active than the parent compound. It, therefore, concluded that in this way, we can not only enhance the solubility of the drug and increase its bioactivity, but also reduce the risk of stomach cancer.

Keywords: Flurbiprofen, microemulsion, surfactants, hyrazides

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Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

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Authors: Ritu Shitak

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Humans are social mammals, of the primate order. Our biology, behaviour, and pathologies are unique to us. In our desire to understand, reduce solitary confinement one source of information is the many reports of social isolation of other social mammals, especially primates. A behavioural study was conducted in the department of pharmacology at Indira Gandhi Medical College, Shimla in Himachal Pradesh province in India using white albino mice. Different behavioural parameters were observed by using open field, tail suspension, tests for aggressive behaviour and social interactions and the effect of isolation was studied. The results were evaluated and the standard statistics were applied. The said study was done to establish facts that isolation itself impairs social behaviour and can lead to alcohol dependence as well as related drug dependence.

Keywords: social isolation, albino mice, drug dependence, isolation on social behaviour

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Authors: Olusola Omolola Olafuyi, Michael Coleman, Raj Kumar Singh Badhan

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Introduction: Malaria in pregnancy has morbidity and mortality implication on both mother and unborn child. Piperaquine (PQ) based antimalarial treatment is emerging as a choice antimalarial for pregnant women in the face of resistance to current antimalarial treatment recommendation in pregnancy. Physiological and biochemical changes in pregnant women may affect the pharmacokinetics of the antimalarial drug in these. In malaria endemic regions other infectious diseases like HIV/AIDs are prevalent. Pregnant women who are co-infected with malaria and HIV/AID are at even more greater risk of death not only due to complications of the diseases but also due to drug-drug interactions (DDIs) between antimalarials (AMT) and antiretroviral (ARVs). In this study, physiologically based pharmacokinetic (PBPK) modelling was used to investigate the effect of physiological and biochemical changes on the impact of ARV mediated DDIs in pregnant women in three countries. Method: A PBPK model for PQ was developed on SimCYP® using published physicochemical and pharmacokinetic data of PQ from literature, this was validated in three customized population groups from Thailand, Sudan and Papua New Guinea with clinical data. Validation of PQ model was also done in presence of interaction with efavirenz (pre-validated on SimCYP®). Different albumin levels and pregnancy stages was simulated in the presence of interaction with standard doses of efavirenz and ritonavir. PQ day 7 concentration of 30ng/ml was used as the efficacy endpoint for PQ treatment.. Results: The median day 7 concentration of PQ remained virtually consistent throughout pregnancy and were satisfactory across the three population groups ranging from 26-34.1ng/ml; this implied the efficacy of PQ throughout pregnancy. DDI interaction with ritonavir and efavirenz resulted in modest effect on the day 7 concentrations of PQ with AUCratio ranging from 0.56-0.8 and 1.64-1.79 for efavirenz and ritonavir respectively over 10-40 gestational weeks, however, a reduction in human serum albumin level reflective of severe malaria resulted in significantly reduced the number of subjects attaining the PQ day 7 concentration in the presence of both DDIs. The model demonstrated that the DDI between PQ and ARV in pregnant women with different malaria severities can alter the pharmacokinetic of PQ.

Keywords: antiretroviral, malaria, piperaquine, pregnancy, physiologically-based pharmacokinetics

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Authors: Londeka Ntuli, Frasia Oosthuizen

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Background: Tenefovir disiproxil fumarate (TDF) is a nephrotoxic drug and has been proven to contribute to renal insufficiency necessitating intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. TDF is one of the preferred first-line drugs used in combination therapy in most regions. There are estimated 300 000 patients being initiated on the Efavirenz/TDF/Emtricitabine first-line regimen annually in South Africa. It is against this background that this study aims to investigate the effects of TDF on renal sufficiency of HIV positive patients. Methodology: A retrospective quantitative study was conducted, analysing clinical charts of HIV positive patient’s older than 18 years of age and on a TDF-containing regimen for more than 1 year. Data were obtained from the analysis of patient files and was transcribed into Microsoft® Excel® spreadsheet. Extracted data were coded, categorised and analysed using STATA®. Results: A total of 275 patient files were included in this study. Renal function started decreasing after 3 months of treatment (with 93.5% patients having a normal EGFR), and kept on decreasing as time progressed with only 39.6% normal renal function at year 4. Additional risk factors for renal insufficiency included age below 25, female gender, and additional medication. Conclusion: It is clear from this study that the use of TDF necessitates intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. The findings from this study generated pertinent information on the safety profile of the drug TDF in a resource-limited setting of a public health institution. The appropriate management is of tremendous importance in the South African context where the majority of HIV positive individuals are on the TDF containing regimen; thus it is beneficial to ascertain the possible level of toxicities these patients may be experiencing.

Keywords: renal insufficiency, tenefovir, HIV, risk factors

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Authors: Mattia Testuzza

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

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

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Authors: Salwa Mohamed Salah Eldin, Howida Kamal Ibrahim

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Introduction: Major depressive disorder affects high proportion of the world’s population presenting cost load in health care. Extended release venlafaxine is more convenient and could reduce discontinuation syndrome. The once daily dosing also reduces the potential for adverse events such as nausea due to reduced Cmax. Venlafaxine is an effective first-line agent in the treatment of depression. A once daily formulation was designed to enhance patient compliance. Complexing with a resin was suggested to improve loading of the water soluble drug. The formulated systems were thoroughly evaluated in vitro to prove superiority to previous trials and were compared to the commercial extended release product in experimental animals. Materials and Methods: Venlafaxine-resinates were prepared using Dowex®50WX4-400 and Dowex®50WX8-100 at drug to resin weight ratio of 1: 1. The prepared resinates were evaluated for their drug content, particle shape and surface properties and in vitro release profile in gradient pH. The release kinetics and mechanism were evaluated. Venlafaxine-Dowex® resinates were encapsulated using O/W solvent evaporation technique. Poly-ε-caprolactone, Poly(D, L-lactide-co-glycolide) ester, Poly(D, L-lactide) ester and Eudragit®RS100 were used as coating polymers alone and in combination. Drug-resinate microcapsules were evaluated for morphology, entrapment efficiency and in-vitro release profile. The selected formula was tested in rabbits using a randomized, single-dose, 2-way crossover study against Effexor-XR tablets under fasting condition. Results and Discussion: The equilibrium time was 30 min for Dowex®50WX4-400 and 90 min for Dowex®50WX8-100. The percentage drug loaded was 93.96 and 83.56% for both resins, respectively. Both drug-Dowex® resintes were efficient in sustaining venlafaxine release in comparison to the free drug (up to 8h.). Dowex®50WX4-400 based venlafaxine-resinate was selected for further encapsulation to optimize the release profile for once daily dosing and to lower the burst effect. The selected formula (coated with a mixture of Eudragit RS and PLGA in a ratio of 50/50) was chosen by applying a group of mathematical equations according to targeted values. It recorded the minimum burst effect, the maximum MDT (Mean dissolution time) and a Q24h (percentage drug released after 24 hours) between 95 and 100%. The 90% confidence intervals for the test/reference mean ratio of the log-transformed data of AUC0–24 and AUC0−∞ are within (0.8–1.25), which satisfies the bioequivalence criteria. Conclusion: The optimized formula could be a promising extended release form of the water soluble, short half lived venlafaxine. Being a multiple unit formulation, it lowers the probability of dose dumping and reduces the inter-subject variability in absorption.

Keywords: biodegradable polymers, cation-exchange resin, microencapsulation, venlafaxine hcl

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Authors: Emy Nayana Pinto, Denise Bomtempo Birche De Carvalho

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In the present study, the harmful use of illicit drugs is seen as a public health problem and as one of the expressions of the social question, since its consequences fall mainly on the poorer classes of the population. This perspective is a counterpoint to the dominant paradigm on illicit drug policy at the global level, whose centrality lies within the criminal justice arena. The 'drug problem' is internationally combated through fragmented approaches that focus its actions on banning and criminalizing users. In this sense, the research seeks to answer the following key questions: What are the influences of the prohibitionism in the recommendations of the United Nations (UN), the World Health Organization (WHO), and the formulation of drug policies in member countries? What are the actors that have been provoking the prospect of breaking with the prohibitionist paradigm? What is the WHO contribution to the rupture with the prohibitionist paradigm and the displacement of the drug problem in the field of public health? The general objective of this work is to seek evidence from the perspective of rupture with the prohibitionist paradigm in the field of drugs policies at the global and regional level, through analysis of documents of the World Health Organization (WHO), between the years of 2001 to 2016. The research was carried out in bibliographical and documentary sources. The bibliographic sources contributed to the approach with the object and the theoretical basis of the research. The documentary sources served to answer the research questions and evidence the existence of the perspective of change in drug policy. Twenty-two documents of the UN system were consulted, of which fifteen had the contribution of the World Health Organization (WHO). In addition to the documents that directly relate to the subject of the research, documents from various agencies, programs, and offices, such as the Joint United Nations Program on HIV/AIDS (UNAIDS) and the United Nations Office on Drugs and Crime (UNODC), which also has drugs as the central or transversal theme of its performance. The results showed that from the 2000s it was possible to find in the literature review and in the documentary analysis evidence of the critique of the prohibitionist paradigm parallel to the construction of a new perspective for drug policy at the global level and the displacement of criminal justice approaches for the scope of public health, with the adoption of alternative and pragmatic interventions based on human rights, scientific evidence and the reduction of social damages and health by the misuse of illicit drugs.

Keywords: illicit drugs, international organizations, prohibitionism, public health, World Health Organization

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Authors: H. Tayefih, F. farajzade ahari, F. Zarghami, V. Zeighamian, N. Zarghami, Y. Pilehvar-soltanahmadi

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Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly (N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm–MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

Keywords: PNIPAAm-MAA, breast cancer, curcumin, drug delivery

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Authors: Ajmal Khan Kassi, Humayun Javed, Tariq Mukhtar

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The research was conducted to screen out resistance and susceptibility of okra varieties against Helicoverpa armigera under field conditions 2016. In this experiment, the different management practices viz. release Trichogramma chilonis, hoeing, and weeding, clipping, and lufenuron were tested individually and with all possible combinations for the controlling of American bollworm at 3 diverse localities viz. University research farm Koont, National Agriculture Research Centre (NARC) and farmer field Taxila by using resistant variety Arka Anamika. All the treatment combinations regarding damage of shoot and fruit showed significant results. The minimum fruit infestation, i.e., 3.20% and 3.58% was recorded with combined treatment (i.e., T. chilonis + hoeing + weeding + lufenuron) in two different localities. The minimum shoot infestation, i.e., 7.18%, 7.08%, and 6.85% was also observed with (T. chilonis + hoeing + weeding + lufenuron) combined treatment at all three different localities. The above-combined treatment (T. chilonis + hoeing + weeding + lufenuron) also resulted in maximum yield at NARC and Taxila, i.e., 57.67 and 62.66 q/ha respectively. On the basis of combined treatment (i.e., T. chilonis + hoeing + weeding + lufenuron) in three different localities, Arka Anamika variety proved to be comparatively resistant against H. armigera. So this variety is recommended for the cultivation in Pothwar region to get maximum yield and minimum losses against H. armigera.

Keywords: okra, screening, combine treatment, Helicoverpa armigera

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Authors: Vijayakameswara Rao Neralla, Jueun Jeon, Jae Hyung Park

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To develop a potential nanocarrier for diagnosis and treatment of rheumatoid arthritis (RA), we prepared a hyaluronic acid (HA)-5β-cholanic acid (CA) conjugate with an acid-labile ketal linker. This conjugate could self-assemble in aqueous conditions to produce pH-responsive HA-CA nanoparticles as potential carriers of the anti-inflammatory drug methotrexate (MTX). MTX was rapidly released from nanoparticles under inflamed synovial tissue in RA. In vitro cytotoxicity data showed that pH-responsive HA-CA nanoparticles were non-toxic to RAW 264.7 cells. In vivo biodistribution results confirmed that, after their systemic administration, pH-responsive HA-CA nanoparticles selectively accumulated in the inflamed joints of collagen-induced arthritis mice. These results indicate that pH-responsive HA-CA nanoparticles represent a promising candidate as a drug carrier for RA therapy.

Keywords: rheumatoid arthritis, hyaluronic acid, nanocarrier, self-assembly, MTX

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Authors: Shashi Sharma, V. K. Katiyar, Uaday Singh

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The ability to manipulate magnetic particles in fluid flows by means of inhomogeneous magnetic fields is used in a wide range of biomedical applications including magnetic drug targeting (MDT). In MDT, magnetic carrier particles bounded with drug molecules are injected into the vascular system up-stream from the malignant tissue and attracted or retained at the specific region in the body with the help of an external magnetic field. Although the concept of MDT has been around for many years, however, wide spread acceptance of the technique is still looming despite the fact that it has shown some promise in both in vivo and clinical studies. This is because traditional MDT has some inherent limitations. Typically, the magnetic force is not very strong and it is also very short ranged. Since the magnetic force must overcome rather large hydrodynamic forces in the body, MDT applications have been limited to sites located close to the surface of the skin. Even in this most favorable situation, studies have shown that it is difficult to collect appreciable amounts of the MDCPs at the target site. To overcome these limitations of the traditional MDT approach, Ritter and co-workers reported the implant assisted magnetic drug targeting (IA-MDT). In IA-MDT, the magnetic implants are placed strategically at the target site to greatly and locally increase the magnetic force on MDCPs and help to attract and retain the MDCPs at the targeted region. In the present work, we develop a mathematical model to study the capturing of magnetic nanoparticles flowing in a fluid in an implant assisted cylindrical channel under the magnetic field. A coil of ferromagnetic SS 430 has been implanted inside the cylindrical channel to enhance the capturing of magnetic nanoparticles under the magnetic field. The dominant magnetic and drag forces, which significantly affect the capturing of nanoparticles, are incorporated in the model. It is observed through model results that capture efficiency increases from 23 to 51 % as we increase the magnetic field from 0.1 to 0.5 T, respectively. The increase in capture efficiency by increase in magnetic field is because as the magnetic field increases, the magnetization force, which is attractive in nature and responsible to attract or capture the magnetic particles, increases and results the capturing of large number of magnetic particles due to high strength of attractive magnetic force.

Keywords: capture efficiency, implant assisted-magnetic drug targeting (IA-MDT), magnetic nanoparticles, modelling

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Authors: Mihika Shivkumar, Krishna Kumar, C. Perisamy

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3D printing is a method of manufacturing wherein materials, such as plastic or metal, are deposited in layers one on top of the other to produce a three dimensional object. 3D printing is most commonly associated with creating engineering prototypes. However, its applications in the field of human health care have been frequently disregarded. Medical applications for 3D printing are expanding rapidly and are envisaged to revolutionize health care. Medical applications for 3D printing, both present and its potential, can be categorized broadly, including: creation of customized prosthetics tissue and organ fabrication; creation of implants, and anatomical models and pharmaceutical research regarding drug dosage forms. This piece breaks down bioprinting in the healthcare sector. It focuses on the better subtle elements of every particular point, including how 3D printing functions in the present, its impediments, and future applications in the health care sector.

Keywords: bio-printing, prototype, drug delivery, organ regeneration

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Authors: Huafeng Wei

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Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

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