The broad, long-term objective of the proposed research is to develop a rational intravitreal and systemic drug delivery strategy for treatment of cytomegalovirus (CMV) and herpes simplex virus (HSV) infections. In order to accomplish this, the Principal Investigator has employed microdialysis to sample continuously the vitreous compartment in order to obtain detailed pharmacokinetic information. Preliminary information from the experiments conducted by the Investigator indicates the half-life of ganciclovir in the vitreous is two hours in albino rabbits whereas it is 6 hours in pigmented rabbits. The pigmented rabbit will be used for the proposed study. The microdialysis technique and half-life findings form a basis for the development of controlled long-term intravitreal delivery systems for treatment of infections such as CMV retinitis. This project will attempt to prolong the therapeutic levels of acyclovir and ganciclovir from intravitreal injection by entrapping the drug into biodegradable and biocompatible microspheres. Additional specific aims of this project are to elucidate the dose, Na, K ATPase and metabolic energy dependence, if any, of the vitreous elimination kinetics of purine antiviral analogs.
| 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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