Nanostructured lipid carriers engineered for intranasal delivery of teriflunomide in multiple sclerosis: optimization and in vivo studies.

Background: Multiple sclerosis (MS) is one of the most severe autoimmune disorder of the central nervous system (CNS).

Objective: The present research work was aimed to formulate and investigate teriflunomide (TFM)-loaded intranasal (i.n.

Agranulocytosis-Protective Olanzapine-Loaded Nanostructured Lipid Carriers Engineered for CNS Delivery: Optimization and Hematological Toxicity Studies.

Potential risk of agranulocytosis is one of the drug-induced adverse effects of the second-generation antipsychotic agents. The present investigation aimed to formulate and investigate olanzapine (OLZ)-loaded nanostructured lipid carriers (OLZ-NLCs) via intranasal (i.n.

Ameliorative effects of type-A procyanidins polyphenols from cinnamon bark in compound 48/80-induced mast cell degranulation.

Allergic diseases are a significant health concern in developing countries. Type-A procyanidin polyphenols from cinnamon ( Blume) bark (TAPP-CZ) possesses antiasthmatic and antiallergic potential. The present study was aimed at the possible anti-allergic mechanism of TAPP-CZ against the compound 48/80 (C48/80)-induced mast cell degranulation in isolated rat peritoneal mast cells (RPMCs).

Formulation and ex vivo-in vivo evaluation of pH-triggered brimonidine tartrate in situ gel for the glaucoma treatment using application of 3 factorial design.

Context: Short residence time, poor bioavailability and poor permeability are the major problems for conventional eye drops treatment.

Objective: The aim of this article is to develop, optimize and ex vivo-in vivo investigation of brimonidine tartrate in situ gel as compared to marketed eye drops for the treatment of glaucoma.

Materials And Methods: The effect of independent variables, namely concentrations of polymers, on various dependent variables like viscosity at physiological pH and in vitro drug release were studied by using 3 factorial design.

Therapeutic potential of silymarin in chronic unpredictable mild stress induced depressive-like behavior in mice.

Silymarin, a plant-derived polyphenolic flavonoid of Silybum marianum, elicited significant antidepressant-like activity in an acute restraint stress model of depression. It improved monoamines, mainly 5-hydroxytryptamine (5-HT) levels in the cortex, dopamine (DA) and norepinephrine (NE) in the cerebellum in mice. The present study was undertaken to explore the antidepressant potential of silymarin in chronic unpredictable mild stress (CUMS) induced depressive-like behavior in mice, and to find out its probable mechanism(s) of action, mainly neurogenesis, neuroinflammation, and/or oxidative stress.

Silymarin ameliorates experimentally induced depressive like behavior in rats: Involvement of hippocampal BDNF signaling, inflammatory cytokines and oxidative stress response.

Silymarin is a polyphenolic flavonoid of Silybum marianum, exhibited neuroprotection and antidepressant like activity in acute restraint stressed mice. The main objective of the present study is to investigate possible antidepressant like activity of silymarin in experimentally induced depressive behavior in rats. The depressive behaviors were induced in rats by olfactory bulbectomized (OBX) technique.

Telmisartan attenuates diabetes induced depression in rats.

Background: Role of brain renin angiotensin system (RAS) is well understood and various clinical studies have proposed neuroprotective effects of ARB's. It is also assumed that diabetic depression is associated with activation of brain RAS, HPA axis dysregulation and brain inflammatory events. Therefore, the present study was designed to investigate the antidepressant effect of low dose telmisartan (TMS) in diabetes induced depression (DID) in rats.

Dihydropyrimidinone-isatin hybrids as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.

A novel series of substituted N-(2-(2,3-dioxoindolin-1-yl)acetyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide was designed, synthesized and evaluated for in vitro Reverse Transcriptase (RT) inhibitory activity. This series is a combination of peculiar structural features from leading scaffolds of [(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and oxyindole. In vitro screening led to identification of two hybrids (9c and 9d) possessing higher RT inhibitory activity than the standard rilpivirine.

Risk management and statistical multivariate analysis approach for design and optimization of satranidazole nanoparticles.

Rapidly evolving technical and regulatory landscapes of the pharmaceutical product development necessitates risk management with application of multivariate analysis using Process Analytical Technology (PAT) and Quality by Design (QbD). Poorly soluble, high dose drug, Satranidazole was optimally nanoprecipitated (SAT-NP) employing principles of Formulation by Design (FbD). The potential risk factors influencing the critical quality attributes (CQA) of SAT-NP were identified using Ishikawa diagram.

Ferulic acid ameliorates chronic constriction injury induced painful neuropathy in rats.

Objective: This study focuses on the evaluation of phenolic compound ferulic acid (FA, 4-hydroxy-3-methoxycinnamic acid) in the chronic constriction injury (CCI) of sciatic nerve induced neuropathy in rats.

Methods: Thirty-six animals were randomly divided into six groups. Left sciatic nerve was exposed and ligated, animals in the control, standard, and test groups were treated orally with respective drugs for 21 days.

Development of a credible 3D-QSAR CoMSIA model and docking studies for a series of triazoles and tetrazoles containing 11β-HSD1 inhibitors.

Type 2 diabetes mellitus is described by insulin resistance and high fasting blood glucose. Increased levels of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme result in insulin resistance and metabolic syndrome. Inhibition of 11β-HSD1 decreases glucose production and increases hepatic insulin sensitivity.

Synthesis and docking studies of pyrazine-thiazolidinone hybrid scaffold targeting dormant tuberculosis.

The persistence of Mycobacterium tuberculosis (MTB) in dormant stage assists the pathogen to develop resistance against current antimycobactrial drugs. To address this issue, we report herein the synthesis of N-(4-oxo-2 substituted thiazolidin-3 yl) pyrazine-2-carbohydrazide derivatives designed by following the molecular hybridization approach using pyrazine and thiazolidenone scaffolds. The compounds were evaluated against MTB H37Ra and Mycobacterium bovis BCG in dormancy model.

Mechanistic investigation of biopharmaceutic and pharmacokinetic characteristics of surface engineering of satranidazole nanocrystals.

The designing of surface engineered nanocrystals for improved stability and bioavailability is a multivariate process depending on several critical formulation and process variables. The present investigation deals with formulation of stable nanocrystals of poorly soluble satranidazole (SAT) for improving dissolution rate and pharmacokinetic profiling. SAT has low polar surface area, high dose and dosing frequency.

Design, synthesis and in vivo screening of some novel quinazoline analogs as anti-hyperlipidemic and hypoglycemic agents.

A novel series of substituted quinazoline derivatives were designed, synthesized and evaluated for their hypolipidemic activity in cholesterol induced hyperlipidemic rats. In vivo screening concluded that compounds A-4, C-5 and C-6 have shown potent antihyperlipidemic activity by decreasing the plasma level of triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), followed by increase in level of high density lipoprotein (HDL).

Design of selective TACE inhibitors using molecular docking studies: Synthesis and preliminary evaluation of anti-inflammatory and TACE inhibitory activity.

Tumor necrosis factor-α (TNF-α) converting enzyme (TACE) has been considered one of the principal therapeutic targets for the treatment of TNF-dependent pathologies. Several TACE inhibitors have been reported, but none of them has been successfully passed to phase II clinical trials. In the present work, we attempted to design highly selective new non-hydroxamate sulfonamide TACE inhibitors.

Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review.

Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application).

Biosurfactant produced from Actinomycetes nocardiopsis A17: Characterization and its biological evaluation.

This investigation aims to isolate an Actinomycetes strain producing a biosurfactant from the unexplored region of industrial and coal mine areas. Actinomycetes are selected for this study as their novel chemistry was not exhausted and they have tremendous potential to produce bioactive secondary metabolites. The biosurfactant was characterized and further needed to be utilized for pharmaceutical dosage form.

Prophylactic effects of asiaticoside-based standardized extract of Centella asiatica (L.) Urban leaves on experimental migraine: Involvement of 5HT1A/1B receptors.

The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.

Transcutaneous delivery of leflunomide nanoemulgel: Mechanistic investigation into physicomechanical characteristics, in vitro anti-psoriatic and anti-melanoma activity.

The present study is a mechanistic validation of 'proof of concept' of effective topical delivery of leflunomide (LFD) nanoemulgel for localized efficient treatment of psoriatic lesions as well as melanoma affected skin regions. Hyperproliferation of keratinocytes in psoriasis and symbiotic relationship between keratinocytes and melanocytes, justifies the need of dual acting treatment. LFD is recently introduced significantly effective disease modifying anti-rheumatic drug and has been considered valuable for the treatment of psoriatic arthritis as well as melanoma.

Antiallergic effect of piperine on ovalbumin-induced allergic rhinitis in mice.

Context: Allergic rhinitis (AR) is a global health problem that affects a large number of population. Piperine (PIP) has been reported to exhibit anti-inflammatory, anti-histaminic, and immunomodulatory activities; however, its antiallergic profile has not been studied.

Objective: The objective of the study was to investigate the antiallergic potential of PIP in ova-albumin (OVA)-induced AR, mast cell degranulation (MSD), and OVA-induced paw edema.

Identification and Characterization of Hydrolytic Degradation Products of Cefditoren Pivoxil using LC and LC-MS/TOF.

The present research work was carried out to determine stability of cefditoren pivoxil, an orally absorbed prodrug that is rapidly hydrolysed by intestinal esterases to the active cephalosporin cefditoren. Cefditoren was subjected to stress conditions recommended by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use guideline Q1A (R2). Cefditoren pivoxil was susceptible for degradation under acidic, alkaline and neutral hydrolytic conditions while it was stable under photolytic and thermal stress conditions.

Design and Synthesis of Mannich bases as Benzimidazole Derivatives as Analgesic Agents.

Mannich bases were selected for 2D QSAR study to derive meaningful relationship between the structural features and analgesic activity. Using the knowledge of important features a novel series was designed to obtain improved analgesic activity. A series of novel Mannich bases 1-(N-substituted amino)methyl]-2-substituted benzimidazole derivatives were synthesized and were screened for analgesic activity.

Design and Synthesis of Pyrazole-3-one Derivatives as Hypoglycaemic Agents.

Pyrazole-3-one compounds were designed on the basis of docking studies of previously reported antidiabetic pyrazole compounds. The amino acid residues found during docking studies were used as guidelines for the modification of aromatic substitutions on pyrazole-3-one structure. Depending on the docking score, the designed compounds were selectively prioritized for synthesis.

LC, MS and LC-MS/MS studies for the characterization of degradation products of amlodipine.

In the present study, comprehensive stress testing of amlodipine (AM) was carried out according to International Conference on Harmonization (ICH) Q1A(R2) guideline. AM was subjected to acidic, neutral and alkaline hydrolysis, oxidation, photolysis and thermal stress conditions. The drug showed instability in acidic and alkaline conditions, while it remained stable to neutral, oxidative, light and thermal stress.

Acridone-based antitumor agents: a mini-review.

In the past decades, tricyclic acridone ring system has become one of the major research interests of the medicinal chemists due to the biological significance of this moiety in drug design and drug discovery. Acridone scaffold has substantial bio-potential since it possess crucial activities such as antibacterial, antimalarial, antiviral and anti-neoplastic. The diverse biological activity of acridone and its prospective in reversal of multi-drug resistance has attracted attention of medicinal chemists to explore this scaffold especially to treat multi-drug resistance in cancer.