Nano Research

, Volume 8, Issue 2, pp 621–635

Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentallyinduced dry eye syndrome

  • Shengyan Liu
  • Chu Ning Chang
  • Mohit S. Verma
  • Denise Hileeto
  • Alex Muntz
  • Ulrike Stahl
  • Jill Woods
  • Lyndon W. Jones
  • Frank X. Gu
Research Article

DOI: 10.1007/s12274-014-0547-3

Cite this article as:
Liu, S., Chang, C.N., Verma, M.S. et al. Nano Res. (2015) 8: 621. doi:10.1007/s12274-014-0547-3

Abstract

Topical formulations, commonly applied for treatment of anterior eye diseases, require frequent administration due to rapid clearance from the ocular surface, typically through the lacrimal drainage system or through over-spillage onto the lids. We report on a mucoadhesive nanoparticle drug delivery system that may be used to prolong the precorneal residence time of encapsulated drugs. The nanoparticles were formed from self-assembly of block copolymers composed of poly(d, l-lactide) and Dextran. The enhanced mucoadhesion properties were achieved by surface functionalizing the nanoparticles with phenylboronic acid. The nanoparticles encapsulated up to 12 wt.% of Cyclosporine A (CycA) and sustained the release for up to five days at a clinically relevant dose, which led us to explore the therapeutic efficacy of the formulation with reduced administration frequency. By administering CycA-loaded nanoparticles to dry eye-induced mice once a week, inflammatory infiltrates were eliminated and the ocular surface completely recovered. The same once a week dosage of the nanoparticles also showed no signs of physical irritation or inflammatory responses in acute (1 week) and chronic (12 weeks) studies in healthy rabbit eyes. These findings indicate that the nanoparticles may significantly reduce the frequency of administration for effective treatment of anterior eye diseases without causing ocular irritation.

https://static-content.springer.com/image/art%3A10.1007%2Fs12274-014-0547-3/MediaObjects/12274_2014_547_Fig1_HTML.gif

Keywords

biocompatibilitycopolymermucoadhesionnanoparticledrug deliveryophthalmology

Supplementary material

12274_2014_547_MOESM1_ESM.pdf (1.1 mb)
Supplementary material, approximately 1.05 MB.

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Shengyan Liu
    • 1
    • 2
  • Chu Ning Chang
    • 1
  • Mohit S. Verma
    • 1
    • 2
  • Denise Hileeto
    • 3
  • Alex Muntz
    • 3
  • Ulrike Stahl
    • 3
  • Jill Woods
    • 3
  • Lyndon W. Jones
    • 2
    • 3
  • Frank X. Gu
    • 1
    • 2
  1. 1.Department of Chemical EngineeringUniversity of WaterlooWaterlooCanada
  2. 2.Waterloo Institute for NanotechnologyUniversity of WaterlooWaterlooCanada
  3. 3.Centre for Contact Lens ResearchUniversity of WaterlooWaterlooCanada