Biocompatible long-circulating star carboxybetaine polymers

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology

Background:

• Polyethylene glycol (PEG) is widely used to extend nanoparticle circulation but can decompose and elicit immune responses.
• Zwitterionic polymers offer superior resistance to protein adsorption, presenting a potential alternative to PEG.

Purpose of the Study:

• To investigate the biocompatibility and in vivo circulation of star carboxybetaine polymers.
• To evaluate zwitterionic polymers as alternatives to PEG for biomedical applications.

Main Methods:

• Synthesis of four star carboxybetaine polymers with varying molecular weights using atom transfer radical polymerization (ATRP) from a β-cyclodextrin initiator.
• In vivo circulation studies in mice, including repeat injections.
• Assessment of organ tissue damage, inflammation, antibody response, macrophage cell internalization, cell viability, and hemolytic activity.

Main Results:

• The largest star carboxybetaine polymer (123 kDa) achieved a circulation half-life of 40 hours in mice.
• No significant organ damage, inflammation, or increase in anti-PEG antibodies was observed after repeat injections.
• Carboxybetaine polymers demonstrated slow macrophage internalization, high cell viability, and negligible hemolytic activity.

Conclusions:

• Star carboxybetaine polymers exhibit excellent biocompatibility and prolonged circulation, suggesting they are a viable alternative to PEG in drug delivery systems.
• Zwitterionic polymers, in general, show potential for developing advanced drug delivery platforms with reduced immunogenicity.