pH Effect on Particle Aggregation of Vanillin End-Capped Polylactides Bearing a Hydrophilic Group Connected by a Cyclic Acetal Moiety.

To enhance the pH-responsiveness of poly(lactic acid) (PLA) particles, desired vanillin acetal-based initiators were synthesized and functional PLA was initiated at the chain end. PLLA-V6-OEG particles were prepared using polymers with various values of 2400-4800 g/mol. PLLA-V6-OEG was appropriated to achieve a pH-responsive behavior under physiological conditions within 3 min via the six-membered ring diol-ketone acetal. Moreover, it was found that the polymer chain length () influenced the aggregation rate. TiO was selected as the blending agent to improve the aggregation rate. The PLLA-V6-OEG blended with TiO was found to accelerate the aggregation rate compared with that without TiO, and the best ratio of polymer/TiO was 1:1. To study the effect of the chain end for stereocomplex polylactide (SC-PLA) particles, PLLA-V6-OEG and PDLA-V6-OEG were successfully synthesized. The obtained results of SC-PLA particle aggregation implied that the types of chain end and the molecular weight of polymer could influence the aggregation rate. The SC-V6-OEG blended with TiO could not make our target to aggregate under physiological conditions within 3 min. This study motivated us to control the particle aggregation rate under physiological conditions for applying as a target drug carrier which is significantly influenced by not only the molecular weight but also the hydrophilicity of the chain-end as well as the number of acetal bonds.