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 3 particles were prepared using polymers with various M n values of 2400-4800 g/mol. PLLA-V6-OEG 3 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 ( M n ) influenced the aggregation rate. TiO 2 was selected as the blending agent to improve the aggregation rate. The PLLA-V6-OEG 3 blended with TiO 2 was found to accelerate the aggregation rate compared with that without TiO 2 , and the best ratio of polymer/TiO 2 was 1:1. To study the effect of the chain end for stereocomplex polylactide (SC-PLA) particles, PLLA-V6-OEG 4 and PDLA-V6-OEG 4 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 4 blended with TiO 2 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.