Long Circulating Liposomal Camptothecins CAP and EAP

Award Information
Agency:
Department of Health and Human Services
Branch:
N/A
Amount:
$0.00
Award Year:
2001
Program:
STTR
Phase:
Phase I
Contract:
PHS2001-2
Agency Tracking Number:
2R42CA075761-02
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
TIGEN PHARMACEUTICALS
UNIVERSITY OF KENTUCKY, ASTECC BLDG, RM 346, LEXINGTON, KY, 40506
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
N/A
Principal Investigator
 THOMAS BURKE
 (859) 257-2300
 TGBURKE@UKY.EDU
Business Contact
 THOMAS G BURKE
Phone: (606) 257-2300
Email: TGBURKE@POP.UKY.EDU
Research Institution
 NEW YORK UNIVERSITY OF MEDICINE
 NEW YORK UNIVERSITY OF MEDICINE
NEW YORK, NY, 12101
 Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Based on the extensive data generated during the phase I portion of our studies, there is sufficient and compelling information to support the further development of the highly lipophilic and blood-stable topoisomerase inhibitor, DB-67. In part, the pre-clinical and clinical evaluation of DB-67 is currently being supported by the NCI through the RAID program; the RAID program studies focus on the non-targeted, liposomal delivery of DB-67, in which DB-67 is formulated in the bilayer of the liposome vesicle. This phase II STTR proposal focuses on the liposomal delivery of core-loaded DB-67 prodrug esters. Liposomal core-loading is a feature of FDA-approved liposomal products such as Doxil and DaunoXome and tumor-targeting has been documented for these formulations. The phase II studies proposed below focus on a novel approach allowing for the liposomal delivery of core-loaded DB-67 prodrug esters, which will permit tumor targeting and, accordingly, effect lower systemic toxicity to the DB-67 agent. The chemistry of the liposomal carriers will be adjusted in order to optimize the following: drug retention in the particle in circulation; particle targeting to the tumor by passive mechanisms; the controlled, slow and continuous release of the active, S-phase specific agent at the tumor site resulting in optimal anticancer activity with minimal systemic toxicity. Thus, the specific aims are as follows: 1) scale-up synthesis of chemically-activated pro-drug (CAP) and enzymatically-activated pro-drug (EAP) esters of DB-67 which actively load info the aqueous core of liposomes and 2) liposomal core-loading of CAP and EAP DB-67 esters and optimization of drug retention; and 3) in vitro and in vivo evaluation of liposomal core-loading of CAP and EAP DB-67 esters. Ultimately, we will seek formulation(s) that display optimized drug retention and in vivo and in vitro performance. PROPOSED COMMERCIAL APPLICATION: Not Available

* information listed above is at the time of submission.

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