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Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant

Park, Ju Young
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187020246

Abstract Details

2007, PhD, University of Cincinnati, Engineering : Mechanical Engineering.
Intraocular lymphoma (IOL) needs a long term therapy and its treatment protocol has not been well established. A controlled drug release micro-implant, implantable in scleral pocket in the pars plana region of the eye, is considered to treat IOL as it allows sustained release of therapeutic levels of drug for a desired period of time; thus, overcoming the blood-retinal barrier associated with systemic drug delivery. Methotrexate (MTX) is the most commonly used chemotherapeutic agent to treat IOL. 2-Methoxyestradiol (2ME2) is a potent antitumor and antiangiogenesis agent which, unlike other cytotoxic drugs, has minimal toxicity. To establish a treatment method using controlled release implant, 1) therapeutic range of 2ME2 is evaluated by comparing with MTX in proliferation study with human lymphoma cell line; 2) biodegradable microneedle implant is fabricated to obtain sustained release of 2ME2 within the therapeutic range; 3) computational eye model is created to calculate drug distribution and pharmacokinetics. Results show that the drug release rate of the 25% w.t. 2ME2 microneedle implant follows zero order kinetics without significant burst having mean release rate of 0.36 microg/hr over a 90 days period. The efficacy studies of 2ME2 show dose-time dependent growth inhibition of lymphoma cell lines within the range of 0.1 ~ 1 microM. It is expected that the 25% w.t. 2ME2 microneedle implant has 0.36 microM mean vitreous concentration in the human eye. The implant can sustain within the therapeutic range of 2ME2 on lymphoma cell line (0.1 – 1 microM) for around 90 days. Pharmacokinetic evaluation using computational eye model show that the half-life of the MTX in the vitreous is 7.1 hr for the rabbit eye and 13.9 hr for the human eye. In conclusion, sustained-release of 2ME2 using intravitreal biodegradable micro-needle implants, designed to deliver therapeutic levels of 2ME2 for an extended period of time, shows promise for the treatment of IOL.
Dr. Rupak Banerjee (Advisor)
139 p.
Drug delivery; Drug distribution; Biodegradable polymer; Intraouclr implant; Intraoculr cancer; Lymphoma

Recommended Citations

Citations

  • Park, J. Y. (2007). Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187020246

    APA Style (7th edition)

  • Park, Ju Young. Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant. 2007. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187020246.

    MLA Style (8th edition)

  • Park, Ju Young. "Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant." Doctoral dissertation, University of Cincinnati, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187020246

    Chicago Manual of Style (17th edition)

ucin1187020246
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© 2006, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.