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Nano Research 2015, 8(2): 621-635 https://doi.org/10.1007/s12274-014-0547-3
Research Article | Issue | Published: 11 September 2014

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

Show Author's Information Shengyan Liu1,2,  Chu Ning Chang1,  Mohit S. Verma1,2,  Denise Hileeto3,  Alex Muntz3,  Ulrike Stahl3,  Jill Woods3,  Lyndon W. Jones2,3,  Frank X. Gu1,2( )
Department of Chemical EngineeringUniversity of Waterloo, WaterlooN2L 3G1Canada
Waterloo Institute for NanotechnologyUniversity of Waterloo, WaterlooN2L 3G1Canada
Centre for Contact Lens ResearchUniversity of Waterloo, WaterlooN2L 3G1Canada
Keywords:
nanoparticle, drug delivery, biocompatibility, copolymer, mucoadhesion, ophthalmology
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Liu S, Chang CN, Verma MS, et al. Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentallyinduced dry eye syndrome. Nano Research, 2015, 8(2): 621-635. https://doi.org/10.1007/s12274-014-0547-3
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Abstract Full text Electronic supplementary material About this article

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.


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Abstract
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Electronic supplementary material
About this article

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

Show Author's information Shengyan Liu1,2, Chu Ning Chang1, Mohit S. Verma1,2, Denise Hileeto3, Alex Muntz3, Ulrike Stahl3, Jill Woods3, Lyndon W. Jones2,3, Frank X. Gu1,2( )
Department of Chemical EngineeringUniversity of Waterloo, WaterlooN2L 3G1Canada
Waterloo Institute for NanotechnologyUniversity of Waterloo, WaterlooN2L 3G1Canada
Centre for Contact Lens ResearchUniversity of Waterloo, WaterlooN2L 3G1Canada

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.

Keywords: nanoparticle, drug delivery, biocompatibility, copolymer, mucoadhesion, ophthalmology

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Publication history
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Acknowledgements

Publication history

Received: 03 February 2014
Revised: 21 July 2014
Accepted: 26 July 2014
Published: 11 September 2014
Issue date: February 2015

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2014

Acknowledgements

Acknowledgements

The authors would like to acknowledge Erin Ellyse Bedford and Jasper G. Huang for proofreading and editing the manuscript. This work was financially supported by 20/20 Natural Sciences and Engineering Research Council–Ophthalmic Materials Network.

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