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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
PubMed
Summary
This summary is machine-generated.

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.

Keywords:
biodegradabledrug deliveryhyaluronic acidpolymer sciencepolymersomesprotein therapystimuli-responsive release

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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.