Stimuli-responsive polymersomes are promising tools for protein-based therapies, but require deeper understanding and optimization of their pathology-responsive behavior. 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. 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. 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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| http://dx.doi.org/10.2217/nnm-2023-0300 | DOI Listing |
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