Optimizing Enzyme-Responsive Polymersomes for Protein-Based Therapies

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.

Keywords::

• biodegradable
• drug delivery
• hyaluronic acid
• polymer science
• polymersomes
• protein therapy
• stimuli-responsive release

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2023-0300

Author contributions

D Foster and J Larsen were responsible for the conception and design of experiments, analysis and interpretation of the data and revising this work critically for intellectual content. D Foster was responsible for conducting experiments and drafting of the paper; A Cakley assisted in conducting experiments. All authors approved the final version to be published; and agree to be accountable for all aspects of the work.

Acknowledgments

The authors thank D Martin and A Gross at Auburn University for the use of the GM1SV3 cell lines and E Davis for the use of ATR-FTIR spectrophotometer.

Financial disclosure

This work was supported in part by the National Science Foundation CAREER program under NSF Award no. 2047697. Support was also received from Clemson University’s Creative Inquiry program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported in part by the National Science Foundation CAREER program under NSF Award no. 2047697. Support was also received from Clemson University’s Creative Inquiry program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.