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Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
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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.

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Summary
This summary is machine-generated.

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.

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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.