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Protein Release by Controlled Desorption from Transiently Cationic Nanoparticles.

Timothy H Cheung1,2, Chang Xue2,3, Daniel A Kurtz2

  • 1Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, OntarioM5S 3H6, Canada.

ACS Applied Materials & Interfaces
|January 27, 2023
PubMed
Summary

This study introduces a novel nanoparticle platform for controlled protein release from hydrogels, overcoming limitations of traditional encapsulation methods. The system utilizes electrostatic adsorption and tunable nanoparticle charge to manage therapeutic delivery, preserving protein bioactivity.

Keywords:
biomaterialscontrolled releaseelectrostatichydrogelshydrolysisnanoparticlesproteins

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Area of Science:

  • Biomaterials Science
  • Drug Delivery Systems
  • Polymer Chemistry

Background:

  • Traditional nanoparticle encapsulation for hydrogel drug release faces challenges with protein efficiency and denaturation.
  • An encapsulation-free approach is needed to improve protein delivery and maintain therapeutic integrity.

Purpose of the Study:

  • To develop and evaluate a novel nanoparticle-based platform for controlled, encapsulation-free release of anionic proteins from hydrogels.
  • To investigate the role of nanoparticle surface charge dynamics and electrostatic interactions in governing protein release kinetics.

Main Methods:

  • Synthesis of zwitterionic poly(lactide-block-carboxybetaine) copolymers and formulation into nanoparticles with tunable surface charge.
  • Incorporation of nanoparticles into a hyaluronan-based hydrogel matrix containing anionic proteins (transferrin, panitumumab, GM-CSF) or cationic lysozyme.
  • Assessment of protein release profiles based on nanoparticle hydrolytic stability and electrostatic interactions, with *in vitro* bioactivity assays.

Main Results:

  • Nanoparticles exhibited colloidal stability and tunable surface charge decay rates dependent on ester group hydrolytic stability.
  • Dispersing nanoparticles in hydrogels significantly attenuated the release of anionic proteins, with release rates modulated by nanoparticle surface chemistry.
  • Release rates correlated with the hydrolytic stability of nanoparticle surface groups: rapid for fast-hydrolyzing esters, reduced for slow-hydrolyzing bulky esters, and very slow for non-hydrolyzing amides.
  • No significant release attenuation was observed for cationic lysozyme, confirming the importance of electrostatic interactions.

Conclusions:

  • The developed encapsulation-free nanoparticle platform effectively controls the release of anionic protein therapeutics from hydrogels via tunable electrostatic interactions.
  • The release strategy preserves the bioactivity of released proteins, demonstrating its therapeutic potential.
  • This versatile platform offers a promising advancement for the controlled delivery of protein-based therapeutics.