Engineering pH-Responsive Nanocarriers via an Optimized Synthesis of PMOXA-b-PDPA Amphiphilic Diblock Copolymers

pH-responsive nanocarriers have gain significant attention due to their ability to provide controlled cargo delivery with high precision in response to specific stimuli. However, the polymers used in the self-assembly of these nanocarriers must be carefully designed to meet the requirements of bio-relevant delivery. Here, we present an optimized synthesis of poly(2-methyl-2-oxazoline)-block-poly(2-(diisopropylamino)ethyl methacrylate) (PMOXA-b-PDPA) block copolymers tailored for obtaining carriers with vesicle architecture and thin membranes for an improved release behavior. By systematically modifying the synthesis conditions, we obtain a small library of copolymers, focusing on low molecular weight (MW) variants to reduce the membrane thickness of the resulting vesicles. We investigate the impact of membrane thickness on the kinetics and efficiency of cargo release in response to a pH shift from neutral to slightly acidic conditions that are particularly relevant in pathological environments like tumors. Model cargos of varying MWs, including doxorubicin hydrochloride, exhibited differential release profiles under these pH conditions. Together with no cytotoxicity, the thin membrane represents key aspects that support further development of such carriers for therapeutic applications.