April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Charged Nanogels Efficiently Overcome Ocular Biological Barriers
Author Affiliations & Notes
  • Junjie Zhang
    Dpt of Pharmaceutical Science, Henan Eye Institute, Zhengzhou, China
    Department of Pharmaceutical Sciences,
    Thomas Jefferson University, Philadelphia, Pennsylvania
  • Gauri P. Misra
    Department of Pharmaceutical Sciences,
    Thomas Jefferson University, Philadelphia, Pennsylvania
  • Soohan P. Chang
    Thomas Jefferson University, Philadelphia, Pennsylvania
  • Xiaoxun Li
    Department of Pharmaceutical Sciences,
    Thomas Jefferson University, Philadelphia, Pennsylvania
  • Tao L. Lowe
    Department of Pharmaceutical Sciences,
    Thomas Jefferson University, Philadelphia, Pennsylvania
  • Footnotes
    Commercial Relationships  Junjie Zhang, None; Gauri P. Misra, None; Soohan P. Chang, None; Xiaoxun Li, None; Tao L. Lowe, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 429. doi:
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      Junjie Zhang, Gauri P. Misra, Soohan P. Chang, Xiaoxun Li, Tao L. Lowe; Charged Nanogels Efficiently Overcome Ocular Biological Barriers. Invest. Ophthalmol. Vis. Sci. 2011;52(14):429.

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

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Abstract

Purpose: : Ocular drug delivery remains challening due to the multiple barriers imposed by the eye against the penetration of drugs. There is a need to develop novel drug delivery carriers capable of crossing ocular barriers and increasing ocular bioavailability and decreasing both local and systemic cytotoxicity. One of the promising strategies is the use of nanocarriers. Our aim is to develop tunable nanogels for enhanced permeability across ocular biological barriers and sustain release of ocular therapeutics after topical application.

Methods: : Nanogels, consisted of N-isopropylacrylamide (NIPAAm) and 2-hydroxyl methacrylate-lactide-dextran macromer were synthesized in aqueous medium using UV photopolymerization under stirring. The size and morphology of the nanogels were studied by dynamic light scattering (DLS). Three nanogels: (1) without charge (Nano0), (2) cationic (Nano+), and (3) anionic (Nano-) were first labeled with dichlorotriazinylaminofluorescein (DTAF) for tracking. Cytotoxicity of the nanogels to human brain microvascular endothelial cells (HBMVEC) was being studied by MTT cell viability assay. Ex-vivo permeabilities of different charge nanogels across the sclera-choroid-RPE, sclera, and cornea of pig were determined using side-by-side diffusion cells. 70kDa dextran was used as a control. The DTAF-labeled nanogels solution were added to the donor cell while equal volume of transport buffer was added to the receiver cell. The fluorescence intensity in the receiver cell was assayed for 4 h. The DTAF-labeled nanogels in phosphate buffered saline (PBS) were subconjunctivally injected in one eye of rats, while PBS was subconjunctivally injected in the contralateral eye. Distribution of the nanogels in the cornea, lens, retina, sclera, iris-ciliary body, conjunctival, and vitreous was assayed 1 day later.

Results: : The nanogels did not show cytotoxicity to the HBMVEC. Permeability of the three nanogels across the sclera and cornea was significantly higher than the control. The nanogels with anionic charge showed significantly higher permeability across the sclera than the nanogels without charge and with cationic charges. The nanogels reach the cornea, iris-ciliary body, retina, sclera after subconjunctival injection.

Conclusions: : The developed non-toxic nanogels are more permeable across the sclera than cornea. The nanogels have potential to cross the ocular biological barriers and can be used as intraocular drug delivery carriers.

Keywords: drug toxicity/drug effects • sclera 
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