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Published on: February 1, 2019
Optimizing enzyme-responsive polymersomes for protein-based therapies
Dorian Foster1, Alaura Cakley1, Jessica Larsen1,2
1Department of Chemical & Biomolecular Engineering, Center for Nanotherapeutic Strategies in the Central Nervous System, Clemson University, Clemson, SC 29631, USA.
Abstract:
Aims: Stimuli-responsive polymersomes are promising tools for protein-based therapies, but require deeper understanding and optimization of their pathology-responsive behavior. Materials & methods: Hyaluronic acid (HA)-poly(b-lactic acid) (PLA) polymersomes self-assembled from block copolymers of varying molecular weights of HA were compared for their physical properties, degradation and intracellular behavior. Results: Major results showed increasing enzyme-responsivity associated with decreasing molecular weight. The major formulation differences were as follows: the HA(5 kDa)-PLA formulation exhibited the most pronounced release of encapsulated proteins, while the HA(7 kDa)-PLA formulation showed the most different release behavior from neutral. Conclusion: We have discovered design rules for HA-PLA polymersomes for protein delivery, with lower molecular weight leading to higher encapsulation efficiency, greater release and greater intracellular uptake.
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