| Summary: | 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(<span style="font-variant: small-caps;">D,L</span>-lactide)-<i>b</i>-poly(ethylene glycol) (P(D,L)LA<sub>n</sub>-<i>b</i>-PEG<sub>113</sub>) copolymers with varied hydrophobic P(D,L)LA block length <i>n</i> 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<sub>n</sub>-<i>b</i>-PEG<sub>113</sub> copolymers with relatively short P(D,L)LA block (<i>n</i> ≤ 180) are prone to aggregate in water. P(D,L)LA<sub>n</sub>-<i>b</i>-PEG<sub>113</sub> copolymers with <i>n</i> ≥ 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<sub>n</sub>-<i>b</i>-PEG<sub>113</sub> 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<sub>680</sub>-<i>b</i>-PEG<sub>113</sub> and P(D,L)LA<sub>1230</sub>-<i>b</i>-PEG<sub>113</sub> copolymers were formulated and studied. It was observed that DTX-loaded P(D,L)LA<sub>n</sub>-<i>b</i>-PEG<sub>113</sub> (<i>n</i> = 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<sub>n</sub>-<i>b</i>-PEG<sub>113</sub> (<i>n</i> = 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<sub>1230</sub>-<i>b</i>-PEG<sub>113</sub> nanoparticles demonstrate better anticancer performance than free DTX. Favorable freeze-drying conditions for DTX nanoformulation based on P(D,L)LA<sub>1230</sub>-<i>b</i>-PEG<sub>113</sub> particles were also established.
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