Nanoparticles enhance per oral bioavailability of poorly available molecules: epigallocatechin gallate nanoparticles ameliorates cyclosporine induced nephrotoxicity in rats at three times lower dose than oral solution

Epigallocatechin gallate (EGCG) has been proven to have great therapeutic potential in treatment and prophylaxis of various disorders, which are mediated by free radicals and oxidative stress. However, the poor biopharmaceutical properties and pharmacokinetics including poor stability in gastro-intestinal tract, low intestinal permeability and short plasma half life, have hindered its clinical development. In an attempt to overcome the above problems, EGCG was incorporated into PLGA nanoparticles. The nanoparticles were made following modified double emulsion method employing Didodecyldimethylammonium bromide (DMAB) as stabilizer. The particles were of similar to 130 nm size and polydispersity index of similar to 0.196 with encapsulation efficiency of 70% at 25% drug loading (w/w of polymer). The in vivo antioxidant efficacy of the EGCG nanoparticulate formulation was evaluated in a rat model of Cyclosporine (CyA)-induced chronic nephrotoxicity. Intraperitoneal (i.p.) administered EGCG solution was found to be efficacious in reducing the CyA-induced nephrotoxicity as evident form blood urea nitrogen, plasma creatinine and other parameters including plasma and renal malondialdehyde and glutathione levels, whereas orally administered EGCG solution was found to be ineffective. On the other hand, nanoparticulate formulation of EGCG administered per oral was found to be equally efficacious as i.p. administered EGCG solution in ameliorating CyA-induced renal damage at three times reduced dose. Together, these results suggest the potential of biodegradable nanoparticles in improving the therapeutic efficacy of EGCG

A potential therapeutic strategy for diabetes and its complications in the form of co-encapsulated antioxidant nanoparticles (NanoCAPs) of ellagic acid and coenzyme Q10: Preparation and evaluation in streptozotocin induced diabetic rats

Diabetes is a metabolic disorder and is associated with serious complications caused by oxidative stress. The existing therapies only delay or reduce the severity of these complications but cannot completely prevent or reverse them. Antioxidant therapy is one promising alternative strategy to assuage these complications. However, the poor biopharmaceutical properties of many antioxidants limit their use as first line therapies. Here we propose a new therapeutic strategy to treat diabetes using biodegradable nano-co-encapsulated antioxidant particles (NanoCAPs) of ellagic acid (EA) and coenzyme Q(10) (CoQ(10)). The combination of EA and CoQ(10) showed beneficial effects in ameliorating lipid peroxidation, dyslipidemia and in preventing organ damage in streptozotocin induced diabetic rats. Significantly lower dose of EA and CoQ(10) in NanoCAPs showed equal and sometimes more prominent results in comparison to simple suspension suggesting improved efficacy Additionally, a statistically significant increase was observed in plasma insulin levels with nanoparticulate formulation of EA and CoQ(10) combination in comparison to simple suspension of EA, CoQ(10) alone or in combination as well as CoQ(10) nanoparticles. Collectively, this data indicates the potential use of NanoCAPs of EA and CoQ(10) in diabetes and reducing the associated complications

PLGA nanoparticles stabilized with cationic surfactant : safety studies and application in oral delivery of paclitaxel to treat chemical-induced breast cancer in rat

Purpose This study was carried out to formulate poly(lactide-co-glycolide) (PLGA) nanoparticles using a quaternary ammonium salt didodecyl dimethylammonium bromide (DMAB) and checking their utility to deliver paclitaxel by oral route. Methods Particles were prepared by emulsion solvent diffusion evaporation method. DMAB and particles stabilized with it were evaluated by MTT and LDH cytotoxicity assays. Paclitaxel was encapsulated in these nanoparticles and evaluated in a chemical carcinogenesis model in Sprague Dawley rats. Results MTT and LDH assays showed the surfactant to be safe to in vitro cell cultures at concentrations <33 μM. PLGA nanoparticles prepared using this stabilizer were also found to be non-toxic to cell lines for the duration of the study. When administered orally to rats bearing chemically induced breast cancer, nanoparticles were equally effective/better than intravenous paclitaxel in cremophor EL at 50% lower dose. Conclusions This study proves the safety and utility of DMAB in stabilizing preformed polymers like PLGA resulting in nanoparticles. This preliminary data provides a proof of concept of enabling oral chemotherapy by efficacy enhancement for paclitaxel

Effect of crosslinking agents on chitosan microspheres in controlled release of diclofenac sodium

In this work chitosan microspheres were prepared by the simple coacervation method and crosslinked using epichlorhydrin or glutaraldehyde for the controlled release of diclofenac sodium. The effects of the crosslinking agents on chitosan microspheres over a 12-hour period were assessed with regard to swelling, hydrolysis, porosity, crosslinking, impregnation of diclofenac sodium (DS), and consequently to the release of DS in buffer solutions, simulating the gastrointestinal tract. The degree of swelling varied with the pH for glutaraldehyde chitosan microspheres (GCM) and epichlorhydrin chitosan microspheres (ECM). Partial acid and basic hydrolysis affected the swelling behavior of the GCM matrix. Release kinetics of diclofenac sodium from these matrices were investigated at pH 1.2, 6.8 and 9.0, simulating the gastrointestinal tract conditions. The results indicated that the release mechanism deviated slightly from Fickian transport