Development of Raloxifene Hydrochloride Loaded mPEG-PLA Nanoparticles for Oral Delivery

Abstract:

Objectives: Raloxifene hydrochloride is used in the treatment of breast cancer which suffers from poor bioavailability problem i.e., only 2% due to excessive first pass metabolism. Development of a delivery system to overcome its bioavailability problem can be done by using mPEG-PLA polymeric nanoparticles which has many scientific applications. Methods: mPEG-PLA polymer has been prepared and evaluated using NMR, FTIR and GPC. Nanoparticles were prepared using emulsion-diffusion-evaporation technique and drug release patterns were evaluated. Pharmacokinetic study was done using Sprague dawley rats to increase the drugs bioavailability. Analytical method was developed with an LOQ 0.5 μg/ml and LOD 0.167 μg/ml. Results: Nanoparticles were formulated using synthesized mPEG-PLA polymer has a particle size range of 165-180 nm. In vitro release study showed, about 72% of drug was released from nanoparticles over the given time duration and showed sustained release for 20 days following Higuchi kinetics. Pharmacokinetic study showed that drug loaded nanoparticles were having approximately 4.87 times more bioavailability than the free drug. Conclusion: Raloxifene hydrochloride loaded nanoparticles prepared with the synthesized mPEGPLA polymer which can release the drug slowly and were suitable for oral delivery. From pharmacokinetic study, it was observed that raloxifene hydrochloride loaded nanoparticles were found to show an increase of relative oral bioavailability to that of raloxifene hydrochloride suspension.

Key words: First pass metabolism, mPEG-PLA, Nanoparticles, Emulsion diffusion evaporation method, Bioavailability and Higuchi diffusion.