Grants and Contracts Details
Description
-- Synthesize, purify and characterize nutlin analogs (Months 1-36)
The in vitro and in vivo studies described in the proposal will require substantial
amounts of material to complete. We will resynthesis each analog to be studied,
on an as needed basis. Additionally, we will prepare specific analogs to evade
any liabilities identified in the course of the studies ¡V ie metabolism
-- Formulate nutlin analogs (Months 1-30)
The in vivo studies will center on local delivery of the analogs to the eye. For
each analog we will develop an optimal formulation from FDA approvable
adjuvants that provides maximal drug delivery with minimal irritation. We will
adjust these formulations for each route as appropriate. If needed, we can also
establish formulations for controlled release.
--Carry out pharmacokinetics studies with nutlin analogs to establish effects of
formulation and route of delivery on exposure in tissues surrounding the eye, the eye
itself, and plasma (Months 1-30)
The in vivo efficacy studies will depend upon selecting the single analog with the
best possible pharmacokinetic properties. We will carry out pharmacokinetics
experiments with each analog/formulation, delivered through each appropriate
route, to establish the relative exposures and guide selection of the optimal
analog/formulation/route. Based upon those studies we will carry out detailed
pharmacokinetic analysis of the optimal combination to establish exposure
systemically and in the target tissue.
--Assist in carrying out pharmacodynamic experiments in model organisms by
carrying out satellite pharmacokinetics studies to establish drug levels in target
tissues. (Months 24-36)
Once we have settled on an optimal analog/formulation/route, we will collaborate
in carrying out pharmacokinetic/pharmacodynamic modeling buy carrying out the
analytical portions of the studies.
Status | Finished |
---|---|
Effective start/end date | 4/1/17 → 1/31/18 |
Funding
- University of Tennessee: $109,516.00
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