Optimizing parameters for the controlled release of drugs from biodegradable nanoparticles

Abstract

Restenosis is a condition of re-narrowing of blood vessel that usually proceeds with angioplasty procedures. Paclitaxel (PCTX) is being administrated as an anti-proliferative therapy for the prevention of restenosis but poses adverse side effects due to high dosage used. Biodegradable polymeric nanoparticles are suitable to act as drug carriers to provide a solution to the problem by means of controlled and targeted drug delivery. PLGA nanoparticles were prepared by solvent evaporation with optimized parameters and the average size obtained ranged from 200 to 250 nm and had an average zeta potential ranged from -12 mV to -32 mV with poly(vinyl alcohol) as stabilizer and sucrose as cryoprotectant. It was found that a variety of parameters such as concentration of constituents, sonication duration and temperature affect the size and zeta potential of the nanoparticles. Model drugs fluorescein diacetate (FDA), rhodamine 6G (RHO) and coumarin 6 (COU) were used as PCTX’s substitute due to their lower costs and higher quantification throughput. Drug encapsulated nanoparticles were subjected to release in PBS pH 7.4, incubated at 37 oC. The amount of PCTX release was quantified with high performance liquid chromatography while the other 3 dyes were quantified by microplate reader. The release profiles of PCTX and RHO saw an initial burst release while fluorescein diacetate had negligible burst release. However, a sustained release was not observed for all nanoparticles after the burst release. Based on parameters optimized and preliminary release data (although not conclusive), biodegradable polymeric nanoparticles has the potential to serve as drug carriers for delivery of therapeutics. However, further drug release studies are required to better conclude the different types of drug release profiles that can be obtained.