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Ocular delivery of peptide ganciclov...

University of Missouri - Kansas City.

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Ocular delivery of peptide ganciclovir prodrugs following subconjunctival injection: Evaluation of episcleral drug delivery approach.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Ocular delivery of peptide ganciclovir prodrugs following subconjunctival injection: Evaluation of episcleral drug delivery approach./
作者:	Kansara, Viral.
面頁冊數:	226 p.
附註:	Adviser: Ashim K. Mitra.
Contained By:	Dissertation Abstracts International68-09B.
標題:	Chemistry, Pharmaceutical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3280863
ISBN:	9780549218975

Ocular delivery of peptide ganciclovir prodrugs following subconjunctival injection: Evaluation of episcleral drug delivery approach.
Kansara, Viral.

Ocular delivery of peptide ganciclovir prodrugs following subconjunctival injection: Evaluation of episcleral drug delivery approach. - 226 p.

Adviser: Ashim K. Mitra.

Thesis (Ph.D.)--University of Missouri - Kansas City, 2007.

Retinal delivery of ganciclovir, an FDA approved nucleoside analog and drug of choice for the treatment of human cytomegalo virus (HCMV) retinitis, has been a challenging task. HCMV retinitis is a vision threatening opportunistic viral infection of the retina which mainly affects immunocompromised patients. Various strategies and routes of administration have been evaluated for retinal delivery of ganciclvoir. However, low efficacy and/or adverse effects associated with current approaches have been major obstacles in front of clinicians as well as pharmaceutical scientists. In recent years, episcleral administration has emerged as a viable approach for ocular drug delivery. Therefore, the overall objective of this dissertation project was to study two important aspects of retinal drug delivery, (a) peptide transporter targeted ganciclovir prodrug approach (b) subconjunctival injection, an episcleral route of administration.

ISBN: 9780549218975Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Ocular delivery of peptide ganciclovir prodrugs following subconjunctival injection: Evaluation of episcleral drug delivery approach.
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245 1 0 $a Ocular delivery of peptide ganciclovir prodrugs following subconjunctival injection: Evaluation of episcleral drug delivery approach.
300 $a 226 p.
500 $a Adviser: Ashim K. Mitra.
500 $a Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5884.
502 $a Thesis (Ph.D.)--University of Missouri - Kansas City, 2007.
520 $a Retinal delivery of ganciclovir, an FDA approved nucleoside analog and drug of choice for the treatment of human cytomegalo virus (HCMV) retinitis, has been a challenging task. HCMV retinitis is a vision threatening opportunistic viral infection of the retina which mainly affects immunocompromised patients. Various strategies and routes of administration have been evaluated for retinal delivery of ganciclvoir. However, low efficacy and/or adverse effects associated with current approaches have been major obstacles in front of clinicians as well as pharmaceutical scientists. In recent years, episcleral administration has emerged as a viable approach for ocular drug delivery. Therefore, the overall objective of this dissertation project was to study two important aspects of retinal drug delivery, (a) peptide transporter targeted ganciclovir prodrug approach (b) subconjunctival injection, an episcleral route of administration.
520 $a An ex vivo model was developed and its implication was evaluated for carrier mediated drug delivery. Using this model, the retinal pigment epithelium (RPE) was identified as a major barrier for ganciclovir delivery following episcleral administration. Various vitamin transporters were identified and characterized in the target tissue (retina) using retinoblastoma cells. Mechanism of cellular uptake and intracellular trafficking of essential vitamins (riboflavin, biotin and folic acid) were studied.
520 $a Functional presence of oligopeptide transporters (OPT) was established on the basolateral side of the RPE. A significant inhibition of transport of a model peptide transporter substrate (glycine-sarcosine) by glycine-proline indicated the presence of OPT on the rabbit RPE. A series of ganciclovir monoester peptide prodrugs were evaluated for episcleral ganciclovir delivery. Among the prodrugs tested valine-ganciclovir, valine-valine-ganciclovir, glycine-valine-ganciclovir and tyrosine-valine-ganciclovir demonstrated the greatest inhibition of glycine-sarcosine, indicating that these prodrugs could be substrates for OPT expressed on rabbit RPE. In vivo vitreal pharmacokinetic studies were performed to delineate ocular disposition of peptide ganciclovir prodrugs following subconjunctival injection. All prodrugs exhibited maximum vitreal concentration values above minimum inhibitory concentration for the treatment of HCMV retinitis, however only valine-valine-gancicovir and glycine-valine-ganciclovir maintain vitreous levels of ganciclovir upto 9 hours. In conclusion, subconjunctival injection of valine-valine-GCV and glycine-valineGCV may achieve and maintain therapeutic vitreal concentration of GCV and therefore seem to be promising candidates for the treatment of HCMV retinitis.
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