Enhanced drug loading capacity of 10-hydroxycamptothecin-loaded nanoparticles prepared by two-step nanoprecipitation method

Abstract

The application of poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelles was dampened by their inherent low drug-loading capability. In this study, a series of new poly(ethylene glycol)/poly(l-lactic acid) (PEG/PLLA) multiblock copolymers were facilely synthesized to obtain excellent nanoparticle drug carrier. The structure and composition of the copolymers were investigated by nuclear magnetic resonance (NMR), fourier transform infrared spectroscopy (FT-IR), and gel permeation chromatography (GPC). PEG/PLLA multiblock copolymers with critical micellar concentration (CMC) of 0.91–5.16 mg/L could self-assemble into stable micelles with average diameters of 83.5–142.5 nm. With the resulting multiblock copolymers, stable micelle structure 10-hydroxycamptothecin (HCPT)-loaded nanoparticles were successfully prepared by a two-step nanoprecipitation method, achieving superior drug loading content (11.7%) as well as satisfactory encapsulation efficiency (77.2%) due to interior-chemistry interaction. HCPT-loaded nanoparticles were characterized in terms of size, size distribution and morphology. The results obtained from X-ray powder diffraction (XRD) measurement suggested that HCPT was molecularly dispersed in nanoparticles. In vitro drug release of HCPT-loaded nanoparticles showed sustained-release profiles and was affected by copolymer composition. Stability studies showed that HCPT-loaded nanoparticles presented excellent stability in simulated physiological environments. These results suggest that PEG/PLLA nanoparticles prepared by two-step nanoprecipitation method are stable and promising candidate for delivery of HCPT.