Long-Circulating Liposomal Camptothecins CAP and EAP

Project: Research project

Project Details

Description

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
StatusFinished
Effective start/end date6/25/038/31/04

Funding

  • National Cancer Institute: $220,324.00

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