Impact of intermolecular drug-copolymer interactions on size and drug release kinetics from pH-responsive polymersomes

pH-sensitive polymersomes are produced from amphiphilic copolymers of the type mPEG-b-(PMMA-ran-PDMAEMA) obtained via ATRP, so that mPEG with molecular masses of 2k and 5kDa forms the corona of a hydrophobic double layer with 22–28% molar content in protonable DMAEMA. Vesicles obtained via dialysis were loaded with curcumin, 2-naphthole, paclitaxel (PTX) and ampicillin sodium salt, and the release kinetics of the latter studied via UV-vis spectrometry as a function of pH. Overall, the release profiles clearly indicated a dopant-sensitive kinetics and, likely, mechanism depending on molecule-copolymer interactions. Infrared spectrometry highlighted the formation of hydrogen bonds and salt bridges that may be responsible for these findings; support for the formation of the latter are obtained comparing the IR spectrum for ampicillin doped-vesicles with the anharmonic vibrational transition of model salt bridges. Importantly, DLS data indicated that our vesicles appeared to remain stable even at pH 4.4 after 48 h and completely releasing ampicillin. The release profiles of co-loaded curcumin/PTX with ampicillin also suggest that desorption rates of water-soluble species can be modulated by the presence of hydrophobic molecules in the double layer, at least at pH 7.4 and 6.4.