In this competing renewal application, the Principal Investigator proposes to study the vitreal pharmacokinetics of ganciclovir, foscarnet, and cidofovir, three antiviral agents used to treat cytomegalovirus. A relatively new procedure, microdialysis, will be used which has the advantage of measuring drug levels in a continuous manner. By using this approach and from the experiments that are planned in pigmented rabbit eyes, it will be possible to more thoroughly determine each drug's ocular kinetics than from using previously methods in which each time interval represented a different group of animals. In addition, the investigator proposes to determine physico-chemical and biological determinants that help to explain ganciclovir's distribution and elimination profile. From this information, the investigator plans to develop approximately eighteen prodrugs that in theory could optimize antiviral therapy by prolonging drug levels in the vitreous.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010659-05
Application #
6180051
Study Section
Special Emphasis Panel (ZRG1-AARR-3 (03))
Program Officer
Dudley, Peter A
Project Start
1996-04-01
Project End
2003-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
5
Fiscal Year
2000
Total Cost
$197,209
Indirect Cost
Name
University of Missouri Kansas City
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
800772162
City
Kansas City
State
MO
Country
United States
Zip Code
64110
Mandal, Abhirup; Pal, Dhananjay; Agrahari, Vibhuti et al. (2018) Ocular delivery of proteins and peptides: Challenges and novel formulation approaches. Adv Drug Deliv Rev 126:67-95
Agrahari, Vibhuti; Agrahari, Vivek; Mandal, Abhirup et al. (2017) How are we improving the delivery to back of the eye? Advances and challenges of novel therapeutic approaches. Expert Opin Drug Deliv 14:1145-1162
Joseph, Mary; Trinh, Hoang M; Cholkar, Kishore et al. (2017) Recent perspectives on the delivery of biologics to back of the eye. Expert Opin Drug Deliv 14:631-645
Mandal, Abhirup; Bisht, Rohit; Rupenthal, Ilva D et al. (2017) Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies. J Control Release 248:96-116
Mandal, Abhirup; Cholkar, Kishore; Khurana, Varun et al. (2017) Topical Formulation of Self-Assembled Antiviral Prodrug Nanomicelles for Targeted Retinal Delivery. Mol Pharm 14:2056-2069
Agrahari, Vibhuti; Agrahari, Vivek; Hung, Wei-Ting et al. (2016) Composite Nanoformulation Therapeutics for Long-Term Ocular Delivery of Macromolecules. Mol Pharm 13:2912-22
Patel, Sulabh P; Vaishya, Ravi; Patel, Ashaben et al. (2016) Optimization of novel pentablock copolymer based composite formulation for sustained delivery of peptide/protein in the treatment of ocular diseases. J Microencapsul 33:103-13
Agrahari, Vibhuti; Mandal, Abhirup; Agrahari, Vivek et al. (2016) A comprehensive insight on ocular pharmacokinetics. Drug Deliv Transl Res 6:735-754
Agrahari, Vibhuti; Agrahari, Vivek; Mitra, Ashim K (2016) Nanocarrier fabrication and macromolecule drug delivery: challenges and opportunities. Ther Deliv 7:257-78
Cholkar, Kishore; Gilger, Brian C; Mitra, Ashim K (2016) Topical delivery of aqueous micellar resolvin E1 analog (RX-10045). Int J Pharm 498:326-34

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