pH triggered and charge attracted nanogel for simultaneous evaluation of penetration and toxicity against skin cancer: In-vitro and ex-vivo study.

The current research is focused to develop and investigate the toxicity and penetration potential of biocompatible chitosan nanogel encapsulating capecitabine by ionic interaction mechanism exhibiting pH triggered transdermal targeting. The nanogel (CPNL) was synthesized by ion gelation mechanism using Pluronic F 127 and surface decoration by Transcutol as non-ionic penetration enhancer. The CPNL possesses fine morphology and nano size range when evaluated by TEM, SEM and DLS analysis with cationic charge and slightly acidic pH assayed by zeta potential and pH analysis. It showed pH responsive drug release characteristics mimicking the skin cancer micro-environment. The MTT assay and apoptotic index of CPNL on HaCaT cell line elaborated optimal cell toxicity and retention on 24h of exposure. The ex-vivo skin penetration analysis exhibited noteworthy diffusion and penetration caliber through concentration depth profile, steady state flux and fluorescent skin imaging on porcine tissue. Overall outcomes suggested CPNL as a potent alternative biocompatible, transdermal nanotherapy against skin cancer displaying significant penetration caliber with enhance toxicity on cancerous cell.

pH Responsive 5-Fluorouracil Loaded Biocompatible Nanogels For Topical Chemotherapy of Aggressive Melanoma.

Combating melanoma via topical route is a highly challenging task due to low selectivity, poor efficacy and impeding biological environment of the skin. In the present study, we engineered a chitosan based pH responsive biodegradable nanogel (FCNGL), encapsulated with 5-FU that was effective even at very low drug doses (0.2% w/v) against melanoma. The FCNGL was synthesized by ion gelation technique exhibited nano-size particle distribution and sustained drug release kinetics. Hemolysis and coagulation analysis revealed high safety whereas MTT and apoptosis assays exhibited the efficacy of FCNGL. DMBA-Croton oil Swiss albino mice model was employed for in vivo assessment followed by gamma scintigraphic screening. Tumor burden and pharmacokinetic antioxidant stress levels along with whole-body gamma scintigraphy imaging using 99 mTc labelled nanogel exhibited selective accumulation in melanoma tumor nodules. The pH responsive behaviour of the nanogels resulted in triggered release of 5-FU in slightly acidic microenvironment, resulting in selective drug accumulation at the melanoma site. Immunohistochemistry (IHC) analysis of tumor showed improvement of subcutaneous layer alignment and regeneration of the epithelial skin layer when compared with standard 5% 5-FU and control mice group. Overall our preclinical data using the FCNGL portends to be a promising platform for efficient and sustained delivery of 5-FU for topical chemotherapy that can result in high efficacy, patient compliance and safety in the clinical set up.

Synthesis and Biological Activities of Oxadiazole Derivatives: A Review.

Recently, there has been wide interest in compounds containing the oxadiazole scaffold because of their unique chemical structure and their broad spectrum of biological properties. This review provides readers with an overview of the main synthetic methodologies for oxadiazoles and of their broad spectrum of pharmacological activities such as, anti-microbial, anti-fungal activity, antiviral, anti-tubercular, anti-inflammatory, anti-convulsant, anti-angiogenic, anti-proliferative, analgesic, anti-oedema and in alzheimer activity, which were reported over the past years.

Metabotropic glutamate receptors: a review on prospectives and therapeutic aspects.

The metabotropic glutamate (mGluRs) receptors are a distinct class of G-protein-coupled receptors that act through activation of phospholipase C and/or inhibition of adenylate cyclase. They encompass seven-transmembrane domain proteins, comprehensively expressed in neuronal and glial cells within the brain, spinal cord and periphery and are involved in controlling pathophysiology of a number of diseases. These receptors may be sorted into three groups based on similarity of amino acid sequence, pharmacology and the transducer pathways they couple. The agonists and antagonists act at the N-terminal glutamate binding site and present a pharmacological strategy to modulate pathogenesis. A number of these compounds are positive or negative allosteric modulators that bind within the receptor transmembrane heptahelical domains. This imparts improved subtype selectivity, improved bioavailability and better drug like properties (e.g. CNS penetration). The mGluRs are presently the focal point of sizeable attention because of their potential as drug targets for the treatment of neurological and psychiatric disorders of the brain including Schizophrenia, Alzheimer's disease, Parkinson's disease, addiction, anxiety, depression, epilepsy and pain. The present review focuses on signal transduction mechanisms implicated to control and functionally upregulate the glutamatergic transmission system. The article also hallmarks agonists and antagonists for mGluRs as pivotal agents to ameliorate an array of neurological and psychiatric disorders.

Design, synthesis, and evaluation of thiazolidinone derivatives as antimicrobial and anti-viral agents.

A series of 1,3-thiazolidin-4-one derivatives were prepared by the reaction of respective aromatic amine, aromatic aldehyde, and thioglycolic acid in dry benzene/toluene. The newly synthesized compounds were characterized on the basis of elemental analysis, IR, (1) HNMR, and mass spectra. The newly synthesized final compounds were evaluated for their in vitro antibacterial, antifungal, and anti-viral activities. Preliminary results indicated that some of the compounds demonstrated antibacterial activity in the range of 7-13 µg/mL, antifungal activity in the range of 13-17 µg/mL, comparable with the standard drugs, ciprofloxacin and fluconazole. Structure-activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro antimicrobial and anti-viral activity of these classes of agents.

Bioconjugation of polymers: a novel platform for targeted drug delivery.

Bioconjugation, a novel technique is usually exploited to improve the biopharmaceutical aspects of a bioactive as well as afford its spatial and temporal distribution. The strategy enlightens newer vistas for delivery of drugs, peptides, enzymes, and oligonucleotides. Site specific delivery may be obtained by tailoring the conjugates as an inactive prodrug and designing polymer drug linkages susceptible to cleavage by specific enzymes or pH. These prodrugs substantially change the mechanisms of cellular entry, pharmacokinetic disposition and ultimately target the drug. The conjugate vehicles are being exploited for targeting pharmacological agents to visceral tissues viz brain, colon etc. These biomaterials are bringing into play, novel drug delivery systems for selectively and specifically ferrying drugs to the desired organ. Noteworthy contributions reported with bioconjugated nanoparticles for biosensing and bioimaging incorporate cell staining, DNA detection, separation and recombination relevance in DNA protection. Only recently, these tailor-made polymers have also gained impetuous for enzyme therapy, gene therapy, insulin therapy, cancer therapy and management of AIDS with the interception of minimal side effects. The present review exhaustively provides an insight to the polymer bioconjugates and their implications for targeted delivery. The article also discusses the therapeutic aspects of these conjugates and that these may serve as fascinating tools for drug delivery.

Metronidazole loaded pectin microspheres for colon targeting.

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit(R) S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug.

High-performance thin layer chromatography method for estimation of conessine in herbal extract and pharmaceutical dosage formulations.

A new, simple, sensitive, precise and robust high-performance thin layer chromatographic (HPTLC) method was developed for the estimation of conessine in herbal extracts and pharmaceutical dosage forms. Analysis of conessine was performed on TLC aluminium plates pre-coated with silica gel 60F-254 as stationary phase. Linear ascending development was carried out in twin trough glass chamber saturated with mobile phase consisting of toluene-ethylacetate-diethyl amine (6.5:2.5:1, v/v/v) at room temperature (25+/-2 degrees C). After derivatized the plate with modified Dragendroff's reagent, Camag TLC scanner III was used for spectrodensitometric scanning and analysis of the plate in absorbance mode at 520 nm. The system was found to give compact spots for conessine (Rf value of 0.82). The data for calibration plots showed good linear relationship with r2=0.9998 in the concentration range of 1-10 microg with respect to peak area. The present method was validated for precision and recovery. The limits of detection and quantification were determined. Statistical analysis of the data showed that the method is reproducible and selective for estimation of conessine.