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Human Scleral Diffusion of Anticancer Drugs from Solution and Nanoparticle Formulation

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Abstract

Purpose

To determine the transscleral permeability of chemotherapeutic drugs vinblastine and doxorubicin for treatment of intraocular tumors, and to compare the use of doxorubicin encapsulated in PLGA and liposome nanoparticles.

Methods

Human sclera was isolated and mounted in a Lucite chamber. Fluorescently tagged vinblastine (VIN), innately fluorescent free doxorubicin (DOX), PLGA doxorubicin (PLGA-DOX), or Doxil (Tibotec Therapeutics) were added to the episcleral donor chamber. The choroidal side was perfused with Balanced Salt Solution. Perfusate fractions were collected over 24 h and measured for fluorescence. Following the experiment, tissue sections were imaged, underwent a drug wash out procedure, and tissue drug content was analyzed using an LC–MS/MS method.

Results

Within 24 h, a total of 68%, 74%, 29%, and 1.9% of the drug dose from VIN, DOX, PLGA-DOX, and Doxil, respectively, diffused across the sclera. VIN and DOX scleral tissue showed strong fluorescence after 24 h. PLGA-DOX displayed scattered fluorescence, and Doxil indicated minimal fluorescence. LC–MS/MS revealed strong tissue binding of DOX.

Conclusions

This study suggests both vinblastine and doxorubicin are able to diffuse across human sclera. In addition, PLGA nanoparticles delivered doxorubicin at a slower rate across the sclera, and the liposome preparation resulted in the slowest delivery of drug.

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ACKNOWLEDGMENTS

This research was supported by grants from Fight for Sight, Research to Prevent Blindness, and NEI Grants: P30 EY06360 and R24 EY017045.

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Authors and Affiliations

  1. Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, USA

    Esther S. Kim, Sung Jin Lee, Dayle H. Geroski & Henry F. Edelhauser

  2. Department of Pharmaceutical Sciences and Ophthalmology, University of Colorado, Denver, Colorado, USA

    Chandrasekar Durairaj, Rajendra S. Kadam & Uday B. Kompella

  3. Department of Ophthalmology, College of Medicine, Soonchunhyang University, Seoul, South Korea

    Sung Jin Lee

  4. Forest Research Insitute, Commack, New York, USA

    Yun Mo

  5. 1365B Clifton Rd. NE, Room B2515, Atlanta, Georgia, 30322, USA

    Esther S. Kim

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  1. Esther S. Kim
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Correspondence to Esther S. Kim.

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Kim, E.S., Durairaj, C., Kadam, R.S. et al. Human Scleral Diffusion of Anticancer Drugs from Solution and Nanoparticle Formulation. Pharm Res 26, 1155–1161 (2009). https://doi.org/10.1007/s11095-009-9835-0

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  • DOI: https://doi.org/10.1007/s11095-009-9835-0

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