pH-sensitive polymersomes: controlling swelling via copolymer structure and chemical composition.
pH-sensitive vesicles used as drug delivery systems (DDSs) are generally composed of protonable copolymers. The disaggregation of these nanoparticles (NPs) during drug release implies the dispersion of positively charged cytotoxic polyelectrolytes in the human body. To alleviate such issue, we synthesised A(BC)n amphiphilic block copolymers with linear (n = 1) and branched (n = 2) architectures to obtain pH-sensitive vesicles capable of releasing drugs in acidic conditions via controlled swelling instead of disaggregation. We obtained this feature by fine-tuning the relative amount of pH-sensitive and hydrophobic monomers. We studied pH-driven swelling by measuring NPs size in neutral and acidic conditions, the latter typical of tumours or inflamed tissues (pH∼6) and lysosomes (pH∼4.5). Dynamic light scattering (DLS) and zeta potential data provided useful indications about the influence of architecture and chemical composition on NPs swelling, stability and polycation release. Results demonstrated that vesicles made of linear copolymers with ∼22-28% in mol of protonable monomers in the 'BC' block swelled more than other species following a pH change from pH 7.4 to pH 4.5. We finally evaluated the cytotoxicity of vesicles composed of linear species, and paclitaxel (PTX) release from the latter in both cancer and normal cells.
['Villani|Simone|S|', 'Adami|Renata|R|', 'Reverchon|Ernesto|E|', 'Ferretti|Anna Maria|AM|', 'Ponti|Alessandro|A|', 'Lepretti|Marilena|M|', 'Caputo|Ivana|I|', 'Izzo|Lorella|L|']
D000972:Antineoplastic Agents, Phytogenic D002470:Cell Survival D056945:Hep G2 Cells D006801:Humans D006863:Hydrogen-Ion Concentration D017239:Paclitaxel D011092:Polyethylene Glycols D011108:Polymers
pH-sensitive polymersomes vesicles ATRP controlled drug-release