Neem gum based pH responsive hydrogel matrix: A new pharmaceutical excipient for the sustained release of anticancer drug.

The present research work was aimed to synthesize neem gum-based site-specific drug delivery device for anticancer drug methotrexate at different pH condition. The hydrogel-based drug delivery device was synthesized by optimizing reaction parameters using a factorial design approach response surface method. This model comprised of various sets of reactions with varying concentrations of solvent, crosslinker, initiator and monomer under microwave radiation. Characterization of the candidate hydrogel was done using UV-visible spectrophotometer, FTIR, SEM, Raman, and XRD techniques. The release profile of the hydrogels network was studied through a methotrexate under different pH conditions. The drug encapsulation capacity was found to be around 93% and 90% in pH 7.4 and 6.8. Drug release through the synthesized hydrogel matrix was found to show non-Fickian behaviour at each medium. The hydrogel network showed less release in pH 6.8 than pH 7.4, suggesting that hydrogels may be suitable drug carriers for release of anticancer drug delivery system. Hemolysis testing was also done to check the compatibility of the synthesized drug delivery device with the four different blood samples. Hemolysis was found to be less than 1% in the case of all blood groups, which indicates that the synthesized candidate polymers are biocompatible with all blood groups.

Anti-proliferate and apoptosis triggering potential of methotrexate-transferrin conjugate encapsulated PLGA nanoparticles with enhanced cellular uptake by high-affinity folate receptors.

The objective of the present study is to enhance the permeation of bioactive molecules across highly lipophilic insurmountable blood brain barrier (BBB) using folic acid (FA) functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles (FA-PNPs) coated with non-ionic surfactant, Polysorbate 80 (P80). The developed Mtx-Tf loaded folic acid anchored PNPs formulation depicted particle size, zeta potential and entrapment efficiency of 109 ± 2.3 nm, -9.38 ± 0.9 mV and 71.0 ± 0.6%, respectively. In vitro release showed biphasic release pattern with initial >35% release in 8 h followed by sustained release, up to 65% by the end of 168 h. SRB cyto-toxicity assay depicted P80-Mtx-Tf-FA-PNPs possessing better cellular cyto-toxicity (C6 Glioma) as compared to counter test formulations, i.e. 100 µM nano-encapsulated drug-conjugate concentration incubated for 72 h resulted in apoptosis of ∼100% of the cellular population. Qualitatively, ∼85% of P80-FITC-FA-PNPs have been found to be internalized by C6 glioma cells post 5 h of incubation. Quantitative cellular uptake assay demonstrated a collinear dependence on drug-conjugate concentration. In vivo administration of P80-Mtx-Tf-FA-PNPs depicted significant decrease, i.e. 73.6% in the tumour spheroid volume. Serum analysis data pointed towards the significant relevance of P80-coated FA-PNPs in lowering the drug diffusion rate by 88.4% (after 30 min) and three-fold enhanced retention time of drug in systemic circulation, thereby felicitating an effective prognostic treatment. This study clearly demonstrated reduced systemic toxicity, enhanced biocompatibility and anti-tumour efficacy of formulated NPs.

Design and Characterization of Apocynin Loaded PLGA Nanoparticles and their In vivo Efficacy in Hyperoxaluric Rats.

BACKGROUND: Apocynin has become a drug of choice in NADPH oxidase induced pathological conditions. Hyperoxaluria is one such pathological condition where NADPH oxidase is involved in eliciting renal injury. OBJECTIVE: Recently apocynin has shown to reverse the transcriptome profile of the NADPH oxidaseassociated genes and reduced oxidative burden in hyperoxaluric animals. The poor solubility of this drug creates certain apprehensions about its bioavailability. PLGA (Poly Lactic co-Glycolic Acid) encapsulation of drug nanoparticles have showed to induce sustain release and henceforth enhance the efficiency and bioavailability of drugs. Therefore, the present study is aimed to envisage a novel approach of synthesizing apocynin doped PLGA nanoparticles. METHODS: The PLGA nanoparticles (both unloaded and loaded) were prepared using solvent extraction method and analyzed for size and stability by Dynamic Light Scattering (DLS), TEM (transmission electron microscopy) and zeta potential. Furthermore, the drug release and encapsulation efficiency of the drug was calculated in vitro. RESULTS: The nanoencapsulation formed was stable with desired size (217-259 nm) and posses a controlled drug release of 20%. Further this nanoencapsulation was explored for its potential to reduce hyperoxaluric manifestations in rats given ethylene glycol with ammonium chloride for 9 days. CONCLUSION: In comparison to free apocynin, it was found that nanoparticles containing apocynin showed moderately better results in vivo by maintaining serum urea and createnine levels. These nanoparticles can be used in diseases where a sustained release of apocynin is required.

Cloud point extraction coupled with microwave-assisted back-extraction (CPE-MABE) for determination of Eszopiclone (Z-drug) using UV-Visible, HPLC and mass spectroscopic (MS) techniques: Spiked and in vivo analysis.

A procedure for the determination of Eszopiclone (ESZ) from complex matrices i.e. in vitro (spiked matrices), as well as in vivo (mice model) was developed using cloud point extraction coupled with microwave-assisted back-extraction (CPE-MABE). Analytical measurements have been carried using UV-Visible, HPLC and MS techniques. The proposed method has been validated according to ICH guidelines and legitimate reproducible and reliability of protocol is assessed through intraday and inter-day precision <3.61% and <4.70%, respectively. Limit of detection has been obtained as 0.083µg/mL and 0.472µg/mL respectively, for HPLC and UV-Visible techniques, corresponding to assessed linearity range. The coaservate phase in CPE was back extracted under microwaves exposure, with isooctane at pre-concentration factor ~50 when 5mL of sample solution was pre-concentrated to 0.1mL. Under optimized conditions i.e. Aqueous-Triton X-114 4% (w/v), pH4.0, NaCl 4% (w/v) and equilibrium temperature of 45°C for 20min, average extraction recovery has been obtained between 89.8 and 99.2% and 84.0-99.2% from UV-Visible and HPLC analysis, respectively. The method has been successfully applied to the pharmacokinetic estimation (post intraperitoneal administration) of ESZ in mice. MS analysis precisely depicted the presence of active N­desmethyl zopiclone in impales as well as in mice plasma.

Surfactant mediated extraction of total phenolic contents (TPC) and antioxidants from fruits juices.

The aim of this study was to enhance the extraction of total phenolic contents (TPC) and antioxidants from fruit juices by the application of surfactants formulations instead of conventional solvents (methanol, ethanol and acetone). A variety of fruit infusions: apple red delicious (apple (rd)) (Malus domestica), Mcintosh apple (apple (i)) (Malus pumila), sweet lemon (Citrus limetta) and mango (Magnifera indica) were studied. Effect of water, organic solvents and five different aqueous surfactant formulations viz. SDS, Brij-35, Brij-58, Triton X-100 and Span-40 were explored for the extraction of TPC and determining the antioxidant activity (AA). The TPC and AA (%) were determined using Folin-Ciocalteu (FCA) and DPPH assay, respectively. The effect of surfactant type, concentration and common organic solvents on the extraction of TPC and AA (%) was studied using UV-visible spectrophotometric technique. Among all the extracting systems employed, Brij-58 showed the highest extraction efficiency.