Nutlin Analogues for the Prevention and Treatment of Proliferative Vitreoretinopathy in Ocular Trauma

Grants and Contracts Details


-- 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.
Effective start/end date4/1/171/31/18


  • University of Tennessee: $109,516.00


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