Development of biocompatible electrostatic‐repulsive microparticles for local tumor treatment

In this study, we reported pH‐responsive microparticles consisting of poly(D,L‐lactide‐co‐glycolide) (PLGA), aminated hyaluronic acid (aHA) conjugated with 2,3‐dimethylmaleic anhydride (DMA, as a pH‐responsive cleavable molecule) (aHA‐DMA), and doxorubicin (DOX, as an antitumor drug) for local tumor treatment. The DOX‐loaded microparticles, denoted as PLGA(aHA‐DMA)/DOX MPs, were fabricated using the W1/O/W2 multi‐emulsification method. These PLGA(aHA‐DMA)/DOX MPs (~10 μm in diameter) accelerated the rate of DOX release at pH 6.8 due to the acidic pH‐responsive cleavage of the DMA moieties followed by electrostatic‐repulsion between aHA and DOX. This event caused the structural destabilization and collapse of the MPs, leading to the rapid release of DOX. Consequently, the PLGA(aHA‐DMA)/DOX MPs resulted in significant inhibition of tumor growth, demonstrating their ability for acidic tumor‐specific treatment.