pH-sensitive polymersomes: controlling swelling via copolymer structure and chemical composition

Area of Science:

• Polymer Chemistry
• Nanotechnology
• Drug Delivery Systems

Background:

• pH-sensitive vesicles for drug delivery often use protonable copolymers.
• Disaggregation of these nanoparticles releases cytotoxic polyelectrolytes.
• A safer alternative is needed for controlled drug release in acidic environments.

Purpose of the Study:

• To synthesize A(BC)n amphiphilic block copolymers for pH-sensitive vesicles.
• To achieve drug release via controlled swelling, not disaggregation, in acidic conditions.
• To investigate the influence of copolymer architecture and composition on vesicle behavior.

Main Methods:

• Synthesis of linear (n=1) and branched (n=2) A(BC)n copolymers.
• Measurement of nanoparticle size changes in response to pH variations (pH 7.4 to 4.5).
• Dynamic light scattering (DLS) and zeta potential analysis to assess swelling, stability, and polycation release.

Main Results:

• Vesicles from linear copolymers with 22-28% protonable monomers exhibited significant swelling at pH 4.5.
• Copolymer architecture and monomer composition influenced nanoparticle swelling and stability.
• Cytotoxicity and paclitaxel release from linear copolymer vesicles were evaluated.

Conclusions:

• Linear A(BC)n copolymers offer a promising strategy for pH-sensitive drug delivery systems.
• Controlled swelling mechanism prevents the release of potentially harmful polyelectrolytes.
• Optimized copolymer composition enables effective drug release in acidic tumor microenvironments or lysosomes.