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Targeted Polymersomes Enable Enhanced Delivery to Peripheral Nerves Post-Injury
Kayleigh Trumbull1, Sophia Fetten2, Noah Arnold1
1Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, South Carolina 29634, United States.
Bioconjugate Chemistry
|March 11, 2025
Summary
Targeted polymersomes offer a novel, noninvasive approach for treating peripheral nerve injuries by overcoming the blood-nerve barrier. Ligands like ApoE and RVG enhance nanoparticle delivery and retention for improved therapeutic outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Regenerative Medicine
Background:
- Peripheral nerve injuries often require invasive surgical repair with variable outcomes, leaving smaller injuries untreated.
- The blood-nerve barrier (BNB) impedes noninvasive drug delivery to nerves, limiting therapeutic options.
- Developing noninvasive strategies to deliver therapeutics across the BNB is crucial for advancing peripheral nerve injury treatment.
Purpose of the Study:
- To investigate the efficacy of ligand-targeted polymersomes for noninvasive delivery across the blood-nerve barrier (BNB) following peripheral nerve injury.
- To compare the nerve targeting and retention capabilities of polymersomes functionalized with apolipoprotein E (ApoE) and rabies virus glycoprotein-based peptide RVG29 (RVG).
- To evaluate the potential of these targeted nanoparticles for enhancing therapeutic payload delivery to injured peripheral nerves.
Main Methods:
- Synthesized polyethylene glycol (PEG)-b-polylactic acid (PLA) polymersomes loaded with AlexaFluor647 dye.
- Conjugated polymersomes with apolipoprotein E (ApoE) or RVG29 peptide (RVG) for targeted delivery.
- Administered untagged, ApoE-tagged, and RVG-tagged polymersomes via intranerve (IN) and intramuscular (IM) injections in a rat sciatic nerve injury model.
- Quantified fluorescence intensity and analyzed pharmacokinetic parameters to assess delivery, penetration, and retention.
Main Results:
- Both ApoE and RVG tags enhanced AlexaFluor647 fluorescence in the nerve injury site after IN injection compared to untagged controls.
- Only RVG-tagged polymersomes significantly increased fluorescence after IM injection, indicating successful nerve penetration.
- Ex vivo analysis revealed that ApoE-tagged polymersomes achieved the highest payload retention irrespective of the injection route.
Conclusions:
- Targeting inflammation with ApoE ligands maximizes polymersome payload retention, while targeting neural cells with RVG ligands promotes greater penetration across the BNB.
- Ligand-functionalized polymersomes represent a promising strategy for noninvasive therapeutic delivery to peripheral nerves.
- This approach holds potential for improving treatment efficacy and accessibility for peripheral nerve injuries.
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