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Engineered assemblies from isomeric pentapeptides augment dry eye treatment.

Yanwen Zhang1, Tinglian Zhou2, Yuzhen Qi1

  • 1Engineering Research Center of Cell & Therapeutic Antibody, Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|December 1, 2023
PubMed
Summary

Subtle peptide sequence changes create diverse nanostructures for drug delivery. These peptide nanocarriers enhance drug retention time on the ocular surface, improving dry eye disease treatment efficacy.

Keywords:
Dry eye diseaseIsomeric peptideMolecular dynamics simulationOcular diseaseSelf-assembly

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Ophthalmology

Background:

  • Peptide sequence modifications influence nanostructure assembly and bioactivity.
  • Understanding how minor sequence changes impact peptide nanocarrier efficacy for drug delivery is crucial.

Purpose of the Study:

  • To investigate the effect of subtle peptide sequence variations on nanostructure morphology and in vivo bioactivity.
  • To evaluate peptide nanocarriers for delivering Diquafosol tetrasodium (DQS) for dry eye disease treatment.

Main Methods:

  • Synthesis of isomeric pentapeptide amphiphiles.
  • Characterization of nanostructure assembly and morphology using techniques like molecular dynamics simulations.
  • In vivo evaluation of drug retention time and therapeutic efficacy on the ocular surface.

Main Results:

  • Isomeric pentapeptide amphiphiles self-assembled into filaments with distinct morphologies.
  • Molecular dynamics simulations confirmed sequence-dependent molecular packing and structural differences.
  • Peptide nanocarriers significantly prolonged Diquafosol tetrasodium retention time on the ocular surface, with efficacy dependent on nanostructure morphology.

Conclusions:

  • Subtle changes in peptide sequences lead to significant alterations in nanostructure formation and in vivo performance.
  • Morphology-dependent drug retention by peptide nanocarriers offers a promising strategy for enhanced ocular drug delivery.
  • These peptide-based nanocarriers demonstrate potential for treating dry eye disease and other ocular conditions due to facile synthesis and biocompatibility.