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PEG-Free Polyion Complex Nanocarriers for Brain-Derived Neurotrophic Factor.

James M Fay1,2, Chaemin Lim1,3, Anna Finkelstein1

  • 1Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7362, USA.

Pharmaceutics
|July 27, 2022
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Summary

Researchers developed new non-poly(ethylene glycol) (PEG) nanoparticles for brain-derived neurotrophic factor (BDNF) therapy. These novel formulations avoid PEG immunogenicity and premature clearance, maintaining therapeutic efficacy.

Keywords:
brain-derived neurotrophic factormicrofluidic mixingnanoformulationpoly(2-oxazoline)poly(ethylene glycol)polyion complex

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Drug Delivery

Background:

  • Poly(ethylene glycol) (PEG) is widely used in therapeutics for stealth properties but can cause immune responses and rapid clearance.
  • Existing polyion complex (PIC) nanoparticles, like Nano-BDNF PEG-PLE, utilize PEG-based polymers, posing challenges for repeated administration.

Purpose of the Study:

  • To develop novel, non-PEG-based polymer alternatives for therapeutic polyion complex (PIC) nanoparticles.
  • To evaluate the self-assembly, characteristics, and receptor interaction of these new PEG-free PIC formulations.

Main Methods:

  • Synthesized two new block copolymers: poly(sarcosine)-b-poly(glutamic acid) (PSR-PLE) and poly(methyl-2-oxazolines)-b-poly(oxazolepropanoic acid)-b-poly(methyl-2-oxazoline) (PMeOx-PPaOx-PMeOx).
  • Formulated nanoparticles using a microfluidic mixer and characterized them using various techniques, including isothermal titration calorimetry.
  • Assessed the interaction of encapsulated brain-derived neurotrophic factor (BDNF) with its receptor kinase.

Main Results:

  • Successfully created novel PEG-free PIC nanoparticles encapsulating BDNF with desirable small size and narrow dispersity.
  • Demonstrated that the new formulations associate via electrostatic interactions and hydrogen bonding, similar to PEG-based PICs.
  • Confirmed that nanoparticle encapsulation does not impede receptor kinase access, preserving BDNF's physiological signaling.

Conclusions:

  • Thoughtful reformulation of PEG-based therapeutic PICs with non-PEG alternatives is feasible.
  • Novel PSR-PLE and PMeOx-PPaOx-PMeOx polymers offer promising alternatives to PEG for developing advanced drug delivery systems.
  • These PEG-free formulations maintain the self-assembly properties and therapeutic potential of PIC nanoparticles.