June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Fabrication of a micellar supramolecular hydrogel for ocular drug delivery
Author Affiliations & Notes
  • zhao liang zhang
    School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wen Zhou, Zhe Jiang, China
  • Hao Chen
    School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wen Zhou, Zhe Jiang, China
  • Xing Yi Li
    School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wen Zhou, Zhe Jiang, China
  • Footnotes
    Commercial Relationships   zhao liang zhang, None; Hao Chen, None; Xing Yi Li, None
  • Footnotes
    Support  Zhejiang Medicines Health Science and Technology Program (Grant No. 2014KYB162)
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1076. doi:
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      zhao liang zhang, Hao Chen, Xing Yi Li; Fabrication of a micellar supramolecular hydrogel for ocular drug delivery. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1076.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Topical instillation of ophthalmic drugs remains a widely accepted topical administration route in the clinical treatment, even though the poor ocular bioavailability after instillation, with less than 5% of the total drug. The unique structural organization of the eye blocking the drug penetration and accelerate the removal of formulation from the ocular surface. This study tried to prepare a micellar supramolecular hydrogel through a simple method that allows more efficient ocular drug delivery.

Methods : The micellar supramolecular was composed of a low-molecular-weight methoxy poly(ethylene glycol) (Mn=2000 Da) block polymer and α-cyclodextrin (α-CD) and prepared by a simple mixing of aqueous block polymer micelles and α-CD aqueous solution. The resultant micellar supramolecular hydrogels were characterized by rheological studies. In vitro cytotoxicity assay using the MTT assay, Draize test, fluorescein staining and histopathological were carried out for biocompatibility study. In vitro drug release and in vivo aqueous humor pharmacokinetics were also conducted.

Results : The micellar supramolecular hydrogels were formed through host-guest inclusion and exhibited thixotropic properties. The hydrogels showed relatively low cytotoxicity towards L-929 and HCEC cells and did not significantly affect the migration of the latter after 24 h incubation. The hydrogel was nonirritant towards the rabbit eye, as indicated by the Draize test fluorescein staining, and histological observation. Nile Red-labeled micellar supramolecular hydrogel showed that it could significantly extend the retention time on the corneal surface in rabbits, compared with the micellar formulation. In vitro release studies indicated that the α-CD concentration strongly influenced the release rate of diclofenac (DIC) from supramolecular hydrogel. In vivo pharmacokinetics indicated that the ocular drug bioavailability of the hydrogel was almost 2 folds than the micellar formulation.

Conclusions : The developed micellar supramolecular hydrogel exhibited relatively low cytotoxicity and could greatly extend the drug retention time on the rabbit corneal surface, significantly improve ocular drug bioavailability. These results suggest that the developed micellar supramolecular hydrogel offers great potential in ocular drug-delivery applications.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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