Highly Stable Docetaxel-Loaded Nanoparticles Based on Poly(D,L-lactide)-b-Poly(ethylene glycol) for Cancer Treatment: Preparation, Characterization, and In Vitro Cytotoxicity Studies

Stability and narrow size distribution are among the main requirements that apply to drug formulations based on polymeric nanoparticles. In this study, we obtained a series of particles based on biodegradable poly( D,L-lactide)-b-poly(ethylene glycol) (P(D,L)LA(n)-b-PEG(113)) copolymers with varied hydrophobic P(D,L)LA block length n from 50 to 1230 monomer units stabilized by poly(vinyl alcohol) (PVA) by a simple "oil-in-water" emulsion method. We found that nanoparticles of P(D,L)LA(n)-b-PEG(113) copolymers with relatively short P(D,L)LA block (n <= 180) are prone to aggregate in water. P(D,L)LA(n)-b-PEG(113) copolymers with n >= 680 can form spherical unimodal particles with values of hydrodynamic diameter less than 250 nm and polydispersity less than 0.2. The aggregation behavior of P(D,L)LA(n)-b-PEG(113) particles was elucidated in terms of tethering density and conformation of PEG chains at the P(D,L)LA core. Docetaxel (DTX) loaded nanoparticles based on P(D,L)LA(680)-b-PEG(113) and P(D,L)LA(1230)-b-PEG(113) copolymers were formulated and studied. It was observed that DTX-loaded P(D,L)LA(n)-b-PEG(113) (n = 680, 1230) particles are characterized by high thermodynamic and kinetic stability in aqueous medium. The cumulative release of DTX from the P(D,L)LA(n)-b-PEG(113) (n = 680, 1230) particles is sustained. An increase in P(D,L)LA block length results in a decrease in DTX release rate. The in vitro antiproliferative activity and selectivity studies revealed that DTX-loaded P(D,L)LA(1230)-b-PEG(113) nanoparticles demonstrate better anticancer performance than free DTX. Favorable freeze-drying conditions for DTX nanoformulation based on P(D,L)LA(1230)-b-PEG(113) particles were also established.