FORMULATION OF CURCUMINOID LOADED SOLID LIPID NANOPARTICLES IN ORDER TO IMPROVE ORAL BIOAVAILABILITY

Objective: Solid lipid nanoparticles (SLNs) of Curcuminoids were formulated and characterized in order to improve poor oral bioavailability of Curcumin. In vivo pharmacokinetics study in rats was conducted to demonstrate improved oral bioavailability.Methods: High pressure homogenization followed by ultrasonication method was adopted to formulate solid lipid nanoparticles of Curcumin. Compritol 888 ATO and Precirol ATO 5 were explored as solid lipids with LIPOID S 75 being used as surfactant. Freeze dried solid lipid nanoparticles were compared with marketed formulation of Curcumin (Adcumin®) in rat plasma using High Pressure Liquid Chromatography (HPLC) method using ultraviolet (UV) detector.Results: Particle size measurements performed on Solid lipid nanoparticles of Curcumin revealed the mean particle size of 200-300 nm for optimized formulations and entrapment efficiency of close to 80%. Sucrose and Dextrose were suitable cryoprotectants to prepare freeze dried solid lipid nanoparticles. Curcumin loaded solid lipid nanoparticles exhibited sustained release pattern during in vitro release kinetics.Conclusion: In vivo pharmacokinetics study in Swiss albino rats revealed that encapsulation of Curcumin into solid lipid nanoparticles increased oral bioavailability of Curcumin to 12 folds when compared with marketed formulation of Raw Curcumin (Adcumin®).Â

DEVELOPMENT AND VALIDATION OF NEW RP-HPLC METHOD FOR THE ESTIMATION OF LINEZOLID IN LINEZOLID GEL

Objective: Development and validation of new RP-HPLC method for the estimation of linezolid in linezolid gel.Methods: Linezolid was chromatographed on a reverse phase symmetry C18 column (150 x 4.6 mm x 3.5 µm) in a mobile phase consisting of potassium dihydrogen phosphate buffer (pH 4.6 adjusted with 10% orthophosphoric acid) and methanol in the ratio of 55:45. The mobile phase was pumped at a flow rate of 1.2 ml/min with detection at 250 nm.Results: The retention time for Linezolid was found about 2.94 min. The detector response was linear in the concentration of 20 µg/ml to 160µg/ml with correlation coefficient of 0.9997. The percentage recovery of Linezolid at target concentration was found to be 97.8%. The limit of detection and limit of quantification was found to be 10 μg/ml and 5 μg/ml respectively. All other validation parameter were within acceptance criteria.Conclusion: The proposed method was found to be simple, fast, accurate, precise and reproducible and could be used for routine quality control analysis of Linezolid in Linezolid gel.Â

Design and Characterization of Buccoadhesive Liquisolid System of an Antihypertensive Drug

Nifedipine is an antihypertensive BCS class II drug which has poor bioavailability when given orally. The objective of the present study was to increase the bioavailability of nifedipine, by formulation and evaluation of a buccoadhesive liquisolid system using magnesium aluminium silicate (Neusilin) as both carrier and coating material and dissolution media were selected based on the solubility studies. A mixture of carboxymethylcellulose sodium and carbomer was used as mucoadhesive polymers. Buccoadhesive tablets were prepared by direct compression. FTIR studies confirmed no interaction between drug and excipients. XRD studies indicated change/reduction in crystallinity of drug. The powder characteristics were evaluated by different flow parameters to comply with pharmacopoeial specifications. The dissolution studies for liquisolid compacts and tablet formulations were carried out and it was found that nifedipine liquisolid tablets formulated from bioadhesive polymers containing 49% liquisolid system, 17.5% carbomer, and 7.5% carboxymethylcellulose sodium showed the best results in terms of dissolution properties. Prepared formulation batches were evaluated for swelling, bioadhesion strength, ex vivo residence time, and permeability studies. The optimized batch was showing promising features of the system. Formulating nifedipine as a buccoadhesive tablet allows reduction in dose and offers better control over the plasma levels

Ulocuplumab (BMS-936564 / MDX1338): a fully human anti-CXCR4 antibody induces cell death in chronic lymphocytic leukemia mediated through a reactive oxygen species-dependent pathway.

The CXCR4 receptor (Chemokine C-X-C motif receptor 4) is highly expressed in different hematological malignancies including chronic lymphocytic leukemia (CLL). The CXCR4 ligand (CXCL12) stimulates CXCR4 promoting cell survival and proliferation, and may contribute to the tropism of leukemia cells towards lymphoid tissues. Therefore, strategies targeting CXCR4 may constitute an effective therapeutic approach for CLL. To address that question, we studied the effect of Ulocuplumab (BMS-936564), a fully human IgG4 anti-CXCR4 antibody, using a stroma--CLL cells co-culture model. We found that Ulocuplumab (BMS-936564) inhibited CXCL12 mediated CXCR4 activation-migration of CLL cells at nanomolar concentrations. This effect was comparable to AMD3100 (Plerixafor--Mozobil), a small molecule CXCR4 inhibitor. However, Ulocuplumab (BMS-936564) but not AMD3100 induced apoptosis in CLL at nanomolar concentrations in the presence or absence of stromal cell support. This pro-apoptotic effect was independent of CLL high-risk prognostic markers, was associated with production of reactive oxygen species and did not require caspase activation. Overall, these findings are evidence that Ulocuplumab (BMS-936564) has biological activity in CLL, highlight the relevance of the CXCR4-CXCL12 pathway as a therapeutic target in CLL, and provide biological rationale for ongoing clinical trials in CLL and other hematological malignancies

Ameliorating effect of olive oil on fertility of male rats fed on genetically modified soya bean

Background: Genetically modified soya bean (GMSB) is a commercialized food. It has been shown to have adverse effects on fertility in animal trials. Extra virgin olive oil (EVOO) has many beneficial effects including anti-oxidant properties. The aim of this study is to elucidate if addition of EVOO ameliorates the adverse effects on reproductive organs of rats fed on GMSB containing diet. Methods: Forty adult male albino rats (150–180 g) of Sprague Dawley strain were separated into four groups of 10 rats each: Group 1 – control group fed on basal ration, Group 2 – fed on basal ration mixed with EVOO (30%), Group 3 – fed on basal ration mixed with GMSB (15%), and Group 4 – fed on basal ration mixed with GMSB (15%) and EVOO (30%). This feeding regimen was administered for 65 days. Blood samples were collected to analyze serum zinc, vitamin E, and testosterone levels. Histopathological and weight changes in sex organs were evaluated. Results: GMSB diet reduced weight of testis (0.66±0.06 vs. 1.7±0.06, p<0.001), epididymis (0.489±0.03 vs. 0.7±0.03, p<0.001), prostate (0.04±0.009 vs. 0.68±0.04, p<0.001), and seminal vesicles (0.057±0.01 vs. 0.8±0.04, p<0.001). GMSB diet adversely affected sperm count (406±7.1 vs. 610±7.8, p<0.001), motility (p<0.001), and abnormality (p<0.001). GMSB diet also reduced serum zinc (p<0.05), vitamin E (p<0.05), and testosterone (p<0.05) concentrations. EVOO diet had no detrimental effect. Addition of EVOO to GMSB diet increased the serum zinc (p<0.05), vitamin E (p<0.05), and testosterone (p<0.05) levels and also restored the weights of testis (1.35±0.16 vs. 0.66±0.06, p<0.01), epididymis (0.614±0.13 vs. 0.489±0.03, p<0.001), prostate (0.291±0.09 vs. 0.04±0.009, p<0.001), seminal vesicle (0.516±0.18 vs. 0.057±0.01, p<0.001) along with sperm count (516±3.1 vs. 406±7.1, p<0.01), motility (p<0.01), and abnormality (p<0.05). Conclusion: EVOO ameliorates the adverse effects of GMSB on reproductive organs in adult male albino rats. This protective action of EVOO justifies its use against the oxidative damage induced by GMSB in reproductive organs

A Review on Liquisolid Systems

Solubility & dissolution rate enhancement from solid oral dosage form is a key issue for current formulation and development. This review discusses, out of several techniques available, liquisolid system to improve dissolution rate of water insoluble drugs and to enhance dissolution rate of water soluble drugs. Different carriers and coating materials like Fujicalin®, Neusilin®, Avicel®, and Aerosil® can be used as carrier materials to prepare liquisolid system. Various non-volatile solvents like propylene glycol, liquid polyethylene glycols, polysorbates, glycerine, N,N-dimethylacetamide and fixed oils can be used to dissolve water insoluble molecules. Liquid drugs can be mixed directly with carriers to produce liquisolid systems. Liquisolid systems can be used to either enhance or retard drug release

Post radiation chylous ascites: a case report

We report a 64 years old gentleman with unresectable right-sided retroperitoneal liposarcoma, who underwent radiotherapy & subsequently developed chylous ascites. He failed conservative management of chylous ascites and this was successfully managed with a peritoneovenous shunt. The pathophysiology and management of post radiational chylous ascites is discussed

Discovery of Novel, Orally Bioavailable, Antileishmanial Compounds Using Phenotypic Screening

Leishmaniasis is a parasitic infection that afflicts approximately 12 million people worldwide. There are several limitations to the approved drug therapies for leishmaniasis, including moderate to severe toxicity, growing drug resistance, and the need for extended dosing. Moreover, miltefosine is currently the only orally available drug therapy for this infection. We addressed the pressing need for new therapies by pursuing a two-step phenotypic screen to discover novel, potent, and orally bioavailable antileishmanials. First, we conducted a high-throughput screen (HTS) of roughly 600,000 small molecules for growth inhibition against the promastigote form of the parasite life cycle using the nucleic acid binding dye SYBR Green I. This screen identified approximately 2,700 compounds that inhibited growth by over 65% at a single point concentration of 10 μM. We next used this 2700 compound focused library to identify compounds that were highly potent against the disease-causing intra-macrophage amastigote form and exhibited limited toxicity toward the host macrophages. This two-step screening strategy uncovered nine unique chemical scaffolds within our collection, including two previously described antileishmanials. We further profiled two of the novel compounds for in vitro absorption, distribution, metabolism, excretion, and in vivo pharmacokinetics. Both compounds proved orally bioavailable, affording plasma exposures above the half-maximal effective concentration (EC50) concentration for at least 12 hours. Both compounds were efficacious when administered orally in a murine model of cutaneous leishmaniasis. One of the two compounds exerted potent activity against trypanosomes, which are kinetoplastid parasites related to Leishmania species. Therefore, this compound could help control multiple parasitic diseases. The promising pharmacokinetic profile and significant in vivo efficacy observed from our HTS hits highlight the utility of our two-step phenotypic screening strategy and strongly suggest that medicinal chemistry optimization of these newly identified scaffolds will lead to promising candidates for an orally available anti-parasitic drug