Fiscal Year:
1990
Title:
POLYMERIC DELIVERY SYSTEMS FOR ANTIRETROVIRAL AGENTS
Agency:
HHS
Contract:
N/A
Award Amount:
$49,855.00
Abstract:
THE GOAL OF THIS PHASE I RESEARCH IS TO DESIGN, SYNTHESIZE, DEVELOP, AND EVALUATE THE IN VITRO EFFICACY OF A NEW CLASS OF POLYMERIC "TARGETED" PRODRUGS OF AZT. THE OVERALL OBJECTIVE OF THIS PROGRAM IS TO CREATE NEW ANTI-AIDS PRODRUGS THAT WILL POSSESS MARKEDLY ENHANCED ANTIVIRAL ACTIVITY, LOW TOXICITY, TARGET ACCESSIBILITY, AND SUSTAINED DRUG RELEASE. THE PHASE I PLAN IS BASED ON THE PROMISING IN VITRO ANTIVIRAL ACTIVITY OBTAINED WITH AZT-POLYMER, CONJUGATE I, AND IS MODELED AFTER PRIOR WORK ON THE DEVELOPMENT OF PT(TRANS-DACH)CARBOXYSACCHARIDE ANTITUMOR COMPLEXES THAT EXHIBITED SUBSTANTIALLY IMPROVED ANTITUMOR PROPERTIES WHEN COMPARED WITH THEIR MONOMERIC ANALOGS. IN PHASE I, ANTIRETROVIRAL PROPERTIES OF AZT CONJUGATE I WILL BE OPTIMIZED, E.G., BY INCREASING THE AZT CONTENT IN THE CONJUGATE. ACTIVITY OF THE CONJUGATES WILL BE EVALUATEDIN VITRO USING HIV AND MURINE RETROVIRUS INFECTION OF T CELLS, MACROPHAGES, AND FIBROBLASTS. AZT-CARBOXYDEXTRAN CONJUGATES WILL BE SYNTHESIZED, EVALUATED, AND OPTIMIZED TO TARGET THE DRUG TO MACROPHAGE CELLS AND FOR INDUCTION OF INTERFERON. IN PHASE II, TWO WELL-CHARACTERIZED MURINE RETROVIRUS MODEL SYSTEMS WILL BE USED TO EVALUATE THE PHARMACOKINETICS AND DYNAMICS OF THE COMPOUNDS AS WELL AS TO DETERMINE THE ABILITY OF POLYMERIC AND MONOMERIC CARRIERS TO TARGET ANTIVIRALS TO SPECIFIC TISSUES. THIS APPROACH OF SUSTAINED SITE-SPECIFIC DELIVERY OF DRUGS VIA BIODEGRADABLE AND BIOCOMPATIBLE POLYMERS CAN BE EXTRAPOLATED TO IMPROVE THE THERAPEUTIC PROPERTIES OF KNOWN ANTI-AIDS DRUGS.
Principal Investigator:
Devinder S Gill
3019531003
Business Contact:
Small Business Information at Submission:
Andrulis Research Corp
11800 Baltimore Ave #113 Beltsville, MD 20705
EIN/Tax ID:
DUNS:
N/A
Number of Employees:
N/A
Woman-Owned:
No
Minority-Owned:
No
HUBZone-Owned:
No