Nanoparticles based on biocompatible methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG₁₁₃-b-P(D,L)LA_n) copolymers as potential vehicles for the anticancer agent oxaliplatin were prepared by a nanoprecipitation technique. It was demonstrated that an increase in the hydrophobic PLA block length from 62 to 173 monomer units leads to an increase of the size of nanoparticles from 32 to 56 nm. Small-angle X-ray scattering studies confirmed the “core-corona” structure of mPEG₁₁₃-b-P(D,L)LA_n nanoparticles and oxaliplatin loading. It was suggested that hydrophilic oxaliplatin is adsorbed on the core-corona interface of the nanoparticles during the nanoprecipitation process. The oxaliplatin loading content decreased from 3.8 to 1.5% wt./wt. (with initial loading of 5% wt./wt.) with increasing PLA block length. Thus, the highest loading content of the anticancer drug oxaliplatin with its encapsulation efficiency of 76% in mPEG₁₁₃-b-P(D,L)LA_n nanoparticles can be achieved for block copolymer with short hydrophobic block.

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-PEG₁₁₃) 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-PEG₁₁₃ copolymers with relatively short P(D,L)LA block (n ≤ 180) are prone to aggregate in water. P(D,L)LA_n-b-PEG₁₁₃ 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-PEG₁₁₃ 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)LA₆₈₀-b-PEG₁₁₃ and P(D,L)LA₁₂₃₀-b-PEG₁₁₃ copolymers were formulated and studied. It was observed that DTX-loaded P(D,L)LA_n-b-PEG₁₁₃ (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-PEG₁₁₃ (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)LA₁₂₃₀-b-PEG₁₁₃ nanoparticles demonstrate better anticancer performance than free DTX. Favorable freeze-drying conditions for DTX nanoformulation based on P(D,L)LA₁₂₃₀-b-PEG₁₁₃ particles were also established.