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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.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Ocular delivery of peptide ganciclovir prodrugs following subconjunctival injection: Evaluation of episcleral drug delivery approach./
Author:	Kansara, Viral.
Description:	226 p.
Notes:	Adviser: Ashim K. Mitra.
Contained By:	Dissertation Abstracts International68-09B.
Subject:	Chemistry, Pharmaceutical. -
Online resource:	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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020 $a 9780549218975
035 $a (UMI)AAI3280863
035 $a AAI3280863
040 $a UMI $c UMI
100 1 $a Kansara, Viral. $3 1021713
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.
590 $a School code: 0134.
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Health Sciences, Ophthalmology. $3 1019445
650 4 $a Health Sciences, Pharmacy. $3 1017737
690 $a 0381
690 $a 0491
690 $a 0572
710 2 $a University of Missouri - Kansas City. $3 1021712
773 0 $t Dissertation Abstracts International $g 68-09B.
790 $a 0134
790 1 0 $a Mitra, Ashim K., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3280863