Berberine mediates tumor cell death by skewing tumor-associated immunosuppressive macrophages to inflammatory macrophages.

Background: Berberine is a plant-derived alkaloid with potent anti-cancer activities. Berberine may redirect the tumor-promoting immunosuppressive M2 macrophages, to tumoricidal activated M1 macrophages. But such an anti-tumor function remains to be demonstrated.

PEGylated microemulsion for dexamethasone delivery to posterior segment of eye.

Dexamethasone (Dex) is one of the most commonly used anti-vascular endothelial growth factor (anti-VEGF) drugs being used in ocular diseases whether it is associated with anterior segment or posterior segment. For diseases of posterior segment of eye, Dex is delivered as intravitreal implant but the route used for the same is very invasive and poses several hazards on long term use. Thus, topical formulation with ability to outreach retina from ocular surface was intended.

Effect of cosurfactant addition on phase behavior and microstructure of a water dilutable microemulsion.

This study reports a detailed characterization of a nonionic microemulsion (μE) composed of n-butylacetate/α-tocopheryl polyethylene glycol succinate (TPGS)/alcohol/water. Two approaches of expanding the monophasic area were explored; (i) addition of Pluronic® 123 (P123) in aqueous phase, and (ii) use of short chain alcohol (CHOH; n = 2-4) as cosurfactant. Pseudo-ternary phase diagrams were constructed using water titration method.

Formulation and In-vivo Pharmacokinetic Consideration of Intranasal Microemulsion and Mucoadhesive Microemulsion of Rivastigmine for Brain Targeting.

Purpose: Presence of tight junctions in blood brain barrier (BBB) pose a major hurdle for delivery of drug and severely affects adequate therapeutic concentration to reach the brain. In present work, we have selected Rivastigmine hydrogen tartrate (RHT), a reversible cholinesterase inhibitor, which exhibits extensive first-pass metabolism, resulting in limited absolute bioavailability (36%). RHT shows extremely low aqueous solubility and poor penetration, resulting in inadequate concentration reaching the brain, thus necessitating frequent oral dosing.

Identification of dual kinase inhibitors of CK2 and GSK3β: combined qualitative and quantitative pharmacophore modeling approach.

PTEN, a tumor suppressor protein, gets deactivated by casein kinase 2 (CK2) and glycogen synthase kinase 3β (GSK3β), which are the major causes of PI3K/AKT-driven tumors. To surmount this problem, the multi-target inhibitor strategy may be of great significance. The goal of this study was to design dual-target inhibitors of CK2 and GSK3β using a combination of pharmacophore modeling and molecular docking studies.

Non-invasive intranasal delivery of quetiapine fumarate loaded microemulsion for brain targeting: Formulation, physicochemical and pharmacokinetic consideration.

Systemic drug delivery in schizophrenia is a major challenge due to presence of obstacles like, blood-brain barrier and P-glycoprotein, which prohibit entry of drugs into the brain. Quetiapine fumarate (QF), a substrate to P-glycoprotein under goes extensive first pass metabolism leading to limited absorption thus necessitating frequent oral administration. The aim of this study was to develop QF based microemulsion (ME) with and without chitosan (CH) to investigate its potential use in improving the bioavailability and brain targeting efficiency following non-invasive intranasal administration.

"Application of Box-Behnken design for optimization and development of quetiapine fumarate loaded chitosan nanoparticles for brain delivery via intranasal route* ".

The objective of the present investigation was to optimize and develop quetiapine fumarate (QF) loaded chitosan nanoparticles (QF-NP) by ionic gelation method using Box-Behnken design. Three independent variables viz., X1-Concentration of chitosan, X2-Concentration of sodium tripolyphosphate and X3-Volume of sodium tripolyphosphate were taken to investigate their effect on dependent variables (Y1-Size, Y2-PDI and Y3-%EE).

Thymidylate synthase enhancer region: Novel allele in Indians.

Background: Thymidylate synthase (TS) is the major target for fluoropyrimidine drugs like 5-Fluorouracil (5-FU). There are polymorphic tandem repeats in the TYMS gene enhancer region (TSER). The number of tandem repeats varies in different populations.

Factors Affecting Inducible Expression of Outer Membrane Protein A (OmpA) of Shigella dysenteriae Type-1 in Lactococcus lactis Using Nisin Inducible Controlled Expression (NICE).

Potential use of Lactococcus lactis (L. lactis) as a heterologous protein expression host as well as for delivery of multiple therapeutic proteins has been investigated extensively using Nisin Inducible Controlled Expression (NICE) system. Optimum inducible expression of heterologous protein by NICE system in L.

Melt-in-Mouth Multi-particulate System for the Treatment of ADHD: A Convenient Platform for Pediatric Use.

Generally, pellets obtained from extrusion/spheronization, containing microcrystalline cellulose (MCC), do not disintegrate. An attempt has been made to develop melt-in-mouth pellets of taste-masked atomoxetine hydrochloride, using extrusion-spheronization, for pediatric patients. Melt-in-mouth pellets were prepared using extrusion-spheronization method and optimized using 3(3) FFD.

Solid lipid nanoparticles (SLN) of Efavirenz as lymph targeting drug delivery system: Elucidation of mechanism of uptake using chylomicron flow blocking approach.

The aim of the present work was to develop a lymph targeted SLN formulation of antiretroviral (ARV) drug and to have an understanding of its underlying mechanism of uptake by the lymphatics. The lymphatics are the inaccessible reservoirs of HIV in human body. Efavirenz (EFV) is a BCS class II, ARV drug that undergoes extensive first pass metabolism.

Impact of Ternary Solvent System in Stability-Indicating Assay Method of Bambuterol: Design of Experiments Approach.

High-performance liquid chromatography method for anti-asthmatic β2-agonist drug bambuterol, its process-related impurities and its major degradation products was developed and validated using quality by design concept. A 3(3) full factorial design was employed to study the effect of three independent factors, namely, ratio of organic modifiers in mobile phase, pH of the buffer and flow rate of the mobile phase. The responses considered were retention time of the last peak and resolution of poorly separated peaks (drug and PR-4 and drug and DP-3).

Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters.

In the present investigation, Quality by Design (QbD) approach was applied on the development and optimization of solid lipid nanoparticle (SLN) formulation of hydrophilic drug rivastigmine (RHT). RHT SLN were formulated by homogenization and ultrasonication method using Compritol 888 ATO, tween-80 and poloxamer-188 as lipid, surfactant and stabilizer respectively. The effect of independent variables (X1 - drug: lipid ratio, X2 - surfactant concentration and X3 - homogenization time) on quality attributes of SLN i.

Stability-indicating assay method for determination of actarit, its process related impurities and degradation products: Insight into stability profile and degradation pathways.

The stability of the drug actarit was studied under different stress conditions like hydrolysis (acid, alkaline and neutral), oxidation, photolysis and thermal degradation as recommended by International Conference on Harmonization (ICH) guidelines. Drug was found to be unstable in acidic, basic and photolytic conditions and produced a common degradation product while oxidative stress condition produced three additional degradation products. Drug was impassive to neutral hydrolysis, dry thermal and accelerated stability conditions.

In vivo Evaluation of Self Emulsifying Drug Delivery System for Oral Delivery of Nevirapine.

Nevirapine is a highly lipophilic and water insoluble non-nucleoside reverse transcriptase inhibitor used for the treatment of HIV-1 infection. Lymphoid tissue constitutes the major reservoir of HIV virus and infected cells in HIV-infected patients. Self-emulsifying drug delivery system, using long chain triglycerides, is a popular carrier of drugs due to their ability to transport lipophilic drugs into the lymphatic circulation.

Lipid based nanoemulsifying resveratrol for improved physicochemical characteristics, in vitro cytotoxicity and in vivo antiangiogenic efficacy.

Resveratrol, a dietary non-flavonoid polyphenolic phytoalexin, has gained attention in cancer chemoprevention. However, poor aqueous solubility and cellular bioavailability has limited its therapeutic application. We formulated a lipid based delivery system of resveratrol with self nanoemulsifying ability.

Investigating the Role of Plasma Glucose Concentration as a Phenotypic Marker for CYP2C9 Genetic Variants, in the Diabetic Population of Gujarat.

The present study was aimed to investigate the role of plasma glucose concentration as a phenotypic marker and to study the frequency distribution of CYP2C9 genetic variants in Gujarat state diabetic population. One hundred and nine unrelated diabetes mellitus patients treated with sulfonylureas were genotyped for CYP2C9*2 and CYP2C9*3 alleles. Their pre- and posttreatment postprandial blood glucose levels were recorded and mean glucose drop per milligram of drug values were calculated and further used as an index for phenotypic correlation.

Self-microemulsifying drug delivery system (SMEDDS)--challenges and road ahead.

Self-microemulsifying drug delivery system (SMEDDS) has emerged as a vital strategy to formulate poor water soluble compounds for bioavailability enhancement. However, certain limitations are associated with SMEDDS formulations which include in vivo drug precipitation, formulation handling issues, limited lymphatic uptake, lack of predictive in vitro tests and oxidation of unsaturated fatty acids. These limitations restrict their potential usage.

Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to irreversible loss of neurons, cognition and formation of abnormal protein aggregates. Rivastigmine, a reversible cholinesterase inhibitor used for the treatment of AD, undergoes extensive first-pass metabolism, thus limiting its absolute bioavailability to only 36% after 3-mg dose. Due to extreme aqueous solubility, rivastigmine shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing.

Investigation of microemulsion system for transdermal delivery of itraconazole.

A new oil-in-water microemulsion-based (ME) gel containing 1% itraconazole (ITZ) was developed for topical delivery. The solubility of ITZ in oils and surfactants was evaluated to identify potential excipients. The microemulsion existence ranges were defined through the construction of the pseudoternary phase diagrams.

Multivariate optimization of formulation and process variables influencing physico-mechanical characteristics of site-specific release isoniazid pellets.

In the present study, isoniazid was formulated as site-specific release pellets with high drug loading (65%, w/w) using extrusion-spheronization followed by aqueous coating of Sureteric (35% weight gain). A statistical experimental strategy was developed to optimize simultaneously the effect of the two formulation variables and one process variable on the critical physico-mechanical properties of the core pellets of isoniazid. Amount of granulating fluid and amount of binder were selected as formulation variables and spheronization speed as a process variable.

Dissolution test for site-specific release isoniazid pellets in USP apparatus 3 (reciprocating cylinder): optimization using response surface methodology.

The present work aims to predict drug release from novel site-specific release isoniazid pellets, in USP dissolution test apparatus 3, using the response surface methodology (RSM). Site-specific release isoniazid pellets were prepared by extrusion-spheronization followed by aqueous coating of Acryl-EZE. RSM was employed for designing of the experiment, generation of mathematical models and optimization study.

Blastocyst implantation failure in mice due to "nonreceptive endometrium": endometrial alterations by Hibiscus rosa-sinensis leaf extract.

Many plants are known to possess antifertility activity. However, limited attempts have been made to scientifically evaluate these claims. Hibiscus rosa-sinensis flowers have been shown to possess antifertility and abortifacient activity.

Olanzapine induced thrombocythemia in Sprague-Dawley rats.

Olanzapine was administered orally (20 mg/kg/day) in Sprague-Dawley rats. Forty-eight male Sprague-Dawley rats were divided into eight groups of six animals each. Four groups of animals received olanzapine for 7, 14, 21 and 48 days.

Restoration of methylmercury inhibited adenosine triphosphatases during vitamin and monothiol therapy.

The aim of our investigation was to examine the efficacy of monothiols and vitamins in the restoration of ion-dependent ATPases in mice intoxicated with methylmercury chloride (MMC). A daily dose of glutathione (GSH), N-acetyl-DL-homocysteine thiolactone (NAHT), vitamin B complex, or vitamin E, either alone or in combination, resulted in significant recovery of N+, K+, Mg++ ATPases. A significant recovery was noted in some therapeutic groups.