(386g) pH-Triggered Polylactie-g-Doxorubicin Nanoparticles With Precisely Controlled High Drug Loading for Targeted Drug Delivery

Nanoscopic size, biodegradability and environmental responsivity are highly desired for drug delivery systems in order to achieve high precision and efficacy in cancer treatment without considerable side effects. In this project, nanoparticles with high drug loading and pH-responsivity were prepared by nanoprecipitation of hydrophobic polymer-drug conjugates. Polymer-drug conjugates, polylactide (PLA)-g-doxorubicin (DOX), were synthesized by click reaction to convert alkyne-functionalized PLA to benzyl aldehyde-functionalized PLA, followed by DOX conjugation to form acid-sensitive Schiff base linkage between drug moieties and polymer scaffold. The DOX loading amount in PLA-g-DOX was determined to be 30 wt% by ¹H NMR and UV spectroscopies. PLA-g-DOX was further used to prepare nanoparticles with precisely controlled drug loading by nanoprecipitaiton in the presence of a PEGylated surfactant. The effects of organic solvent, PLA-g-DOX concentration and PLA-g-DOX/surfactant mass ratio on nanoparticle size and distribution were systematically examined based on DLS and TEM analysis. Nanoparticles prepared under the optimal conditions exhibited well-defined sphere morphology with average diameter around 100 nm. Due to the Schiff base conjugation linkage in PLA-g-DOX, the acid sensitive drug release behavior of the nanoparticles was observed. Cytotoxicity and cell internalization studies of the nanoparticles towards MCF-7 breast cancer cells indicated their promising potential applications as anti-cancer nanomedines.