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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.
Nanomedicine (London, England)
|January 25, 2024
Summary
Hyaluronic acid (HA)-poly(b-lactic acid) (PLA) polymersomes show improved protein delivery with lower molecular weight HA. This enhances encapsulation, release, and cellular uptake for targeted therapies.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Drug Delivery Systems
Background:
- Stimuli-responsive polymersomes are advanced carriers for protein therapeutics.
- Optimizing polymersome behavior for specific pathological conditions is crucial for effective therapy.
- Hyaluronic acid (HA)-poly(b-lactic acid) (PLA) polymersomes offer potential for protein delivery applications.
Purpose of the Study:
- To investigate the relationship between hyaluronic acid (HA) molecular weight and the properties of HA-PLA polymersomes.
- To understand how varying HA molecular weights influence polymersome responsivity, degradation, and protein release kinetics.
- To establish design principles for HA-PLA polymersomes for enhanced protein delivery.
Main Methods:
- Self-assembly of HA-PLA polymersomes using block copolymers with varying HA molecular weights.
- Characterization of physical properties, degradation rates, and enzyme-responsivity of the polymersomes.
- Evaluation of encapsulated protein release profiles and intracellular uptake mechanisms.
Main Results:
- Polymersomes derived from lower molecular weight HA exhibited increased enzyme-responsivity.
- The HA(5 kDa)-PLA formulation demonstrated the most significant protein release.
- The HA(7 kDa)-PLA formulation displayed distinct release behavior compared to neutral conditions.
Conclusions:
- Lower molecular weight HA in HA-PLA polymersomes correlates with higher encapsulation efficiency.
- Reduced HA molecular weight enhances protein release and improves intracellular uptake.
- These findings provide critical design rules for optimizing HA-PLA polymersomes for protein delivery.
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