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Related Concept Videos

Site-Targeted Drug Delivery Systems: Polymeric Carriers01:24

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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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Facile and Efficient Preparation of Tri-component Fluorescent Glycopolymers via RAFT-controlled Polymerization
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Degradable PEGylated Protein Conjugates Utilizing RAFT Polymerization.

Caitlin G Decker1, Heather D Maynard1

  • 1Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive South, Los Angeles, California 90095-1569, United States.

European Polymer Journal
|May 5, 2015
PubMed
Summary
This summary is machine-generated.

Researchers developed degradable poly(ethylene glycol) (PEG) polymers for protein therapeutics. These polymers attach to proteins and can be cleaved, restoring full protein activity and preventing polymer buildup.

Keywords:
controlled radical polymerization (CRP)cyclic ketene acetal (CKA)degradablepoly(ethylene glycol) (PEG)polymer-protein conjugatereversible addition-fragmentation chain transfer (RAFT)

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Area of Science:

  • Polymer Chemistry
  • Bioconjugation
  • Drug Delivery

Background:

  • Poly(ethylene glycol) (PEG)-protein conjugates improve pharmacokinetics but can reduce protein activity and lead to polymer accumulation.
  • Second-generation polymer therapeutics aim to incorporate degradability for improved safety and efficacy.

Purpose of the Study:

  • To synthesize degradable poly(poly(ethylene glycol) methyl ether methacrylate) (pPEGMA) polymers using reversible addition-fragmentation chain transfer (RAFT) polymerization.
  • To create protein-reactive polymers capable of reversible covalent attachment to proteins via a reducible disulfide linkage.
  • To evaluate the hydrolytic degradation of the polymers and the cleavage of the polymer from the protein.

Main Methods:

  • RAFT copolymerization of PEGMA with a cyclic ketene acetal (CKA) monomer (BMDO).
  • Characterization of polymer molecular weight and dispersity using GPC.
  • Analysis of polymer degradation under acidic and basic conditions using 1H-NMR and GPC.
  • Assessment of polymer-protein conjugation and cleavage using gel electrophoresis and mass spectrometry.

Main Results:

  • Two pPEGMA polymers with controlled molecular weights (10.9 and 20.9 kDa) and low dispersities (1.34 and 1.71) were synthesized.
  • The polymers demonstrated hydrolytic degradation under both acidic and basic conditions.
  • Reversible covalent attachment to lysozyme was achieved via a disulfide linkage.
  • Reductive cleavage released lysozyme with restored full activity, and the polymer backbone was shown to be degradable.

Conclusions:

  • A method for synthesizing degradable PEGylated proteins was established.
  • The developed polymers allow for controlled polymer attachment and release, mitigating issues associated with traditional PEGylation.
  • This approach offers a promising strategy for developing advanced polymer therapeutics with enhanced safety and efficacy profiles.