In-vivo study of naltrexone hydrochloride release from an in-situ forming PLGA-PEG-PLGA system in the rabbit

A thermosensitive hydrogel of PLGA-PEG-PLGA triblock synthesized via ring opening polymerization using microwave irradiation method was used to control the release of naltrexone HCl drug. In the present work, the injectable prepared hydrogel was dissolved in phosphate buffer with different amounts of naltrexone hydrochloride. The pharmacokinetic profiles of the drug in rabbits were determined using blood and urine samples after subcutaneous injection of drug formulations (naltrexone hydrochloride solution or naltrexone hydrochloride-hydrogel with doses of 5 and 15 mg/kg body weight). The concentrations of naltrexone HCl and its main metabolite (beta-naltrexol) were determined using a calibrated HPLC analytical method. The samples were collected and analyzed for 14 days. The serum concentrations of naltrexone HCl and β-naltrexol were significantly higher in drug-loaded hydrogels, compared to free injected naltrexone. This phenomenon is attributed to an effective accumulation of naltrexone HCl serum concentration during the process of slow release from hydrogel form (i.e. that amount of newly released naltrexone from hydrogel form, was added to that amount of metabolized drug released previously). As a conclusion, PLGA-PEG-PLGA copolymer can be evaluated as a biodegradable controlled release drug delivery system for naltrexone hydrochloride in the future human studies.

Comparison between naltrexone concentrations in blood after injection of various formulations.