Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant
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2007
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Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187020246 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-ucin11870202462021-08-03T06:12:08Z Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant Park, Ju Young Drug delivery Drug distribution Biodegradable polymer Intraouclr implant Intraoculr cancer Lymphoma 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. 2007-10-08 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187020246 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187020246 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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language |
English |
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topic |
Drug delivery Drug distribution Biodegradable polymer Intraouclr implant Intraoculr cancer Lymphoma |
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Drug delivery Drug distribution Biodegradable polymer Intraouclr implant Intraoculr cancer Lymphoma Park, Ju Young Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant |
author |
Park, Ju Young |
author_facet |
Park, Ju Young |
author_sort |
Park, Ju Young |
title |
Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant |
title_short |
Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant |
title_full |
Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant |
title_fullStr |
Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant |
title_full_unstemmed |
Treatment of Intraocular Lymphoma Using Biodegradable Microneedle Implant |
title_sort |
treatment of intraocular lymphoma using biodegradable microneedle implant |
publisher |
University of Cincinnati / OhioLINK |
publishDate |
2007 |
url |
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187020246 |
work_keys_str_mv |
AT parkjuyoung treatmentofintraocularlymphomausingbiodegradablemicroneedleimplant |
_version_ |
1719432651077582848 |