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An integrated multiscale-multiphysics modeling and simulation of ocular drug delivery with whole-body pharmacokinetic response

Award Number: U01FD005219
ORGANIZATION: FOOD AND DRUG ADMINISTRATION
OPDIV: FDA
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract The majority of blindness and vision impairment in the US are age-related diseases, such as glaucoma and diabetic retinopathy, requiring drug intervention for disease management. The eye has many physical and biological barriers that limit a drug’s bioavailabilty for absorption and restrict systemic drug administration since drug levels required for treatment efficacy may be too toxic to the rest of the body. The complex anatomy and physiology of the eye require highly sophisticated physiologically-based pharmacokinetic (PBPK) model of the eye combined with biophysics-based ocular drug delivery model and whole body pharmacokinetic (PK) and pharmacodynamics (PD) to estimate the PK profile of a drug in the eye after administration. The overall goal of the proposed project is therefore to develop such a unique multiscale- multiphysics model to simulate ocular delivery, absorption, distribution, pharmacokinetics and in vitro to in vivo extrapolation (IVIVE) for generic drugs and drug products. Computational modeling of in vivo ocular drug delivery requires anatomy and physiology of the eye, physicochemical material properties of ocular tissues and barriers as well as physicochemical drug/carrier properties. In Aim 1, high-fidelity models in the form of parametric 2D/3D eye mesh model (human, animal) will be developed, enabling various modes of delivery to be simulated. Aim 2 focuses on the development of a multicompartmental model for ocular drug delivery using a reduced-order model to complement the 3D model from Aim 1. The parameters for the multicompartmental model will be calibrated using the 3D model results and experimental data. It will also be linked to the existing whole body PBPK model. In Aim 3, a database of the fundamental properties of drug products accounting for formulation, morphology, conjugation and interaction with non-biologics will be developed. With the main components developed and integrated, model calibration and validation will be carried out in Aim 4 against available experimental preclinical and clinical data. In Aim 5, mathematical models of typical in vitro transwell-based ocular barriers will be developed, validated, and used in both 3D and compartmental in vivo models to provide a framework for IVIVE. Parametric simulations of drug delivery and PK for brand and generic drugs will be conducted in Aim 6. The novel software tool proposed will be able to provide an accurate and efficient computational platform to virtually test, design, and develop ocular drug products and to facilitate translational applications from bench to bedside, eliminating the high cost and time of in vitro and in vivo experiments.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2016	CFD RESEARCH CORPORATION	6820 MOQUIN DR NW	HUNTSVILLE	AL	35806	MADISON	USA	Food and Drug Administration Research	000	3	3/25/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	CFD RESEARCH CORPORATION	701 MCMILLIAN WAY STE D	HUNTSVILLE	AL	35806	MADISON	USA	Food and Drug Administration Research	000	3	8/25/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $154,169 )
2016	2016	CFD RESEARCH CORPORATION	215 WYNN DR, 5TH FLOOR	HUNTSVILLE	AL	35805	MADISON	USA	Food and Drug Administration Research	000	3	8/24/2016	NON-COMPETING CONTINUATION	$154,169
														Subtotal = $154,169

Issue Date FY: 2015 ( Subtotal = $151,132 )
2015	2015	CFD RESEARCH CORPORATION	215 WYNN DR, 5TH FLOOR	HUNTSVILLE	AL	35805	MADISON	USA	Food and Drug Administration Research	000	2	8/24/2015	NON-COMPETING CONTINUATION	$151,132
														Subtotal = $151,132

Issue Date FY: 2014 ( Subtotal = $148,122 )
2014	2014	CFD RESEARCH CORPORATION	215 WYNN DR, 5TH FLOOR	HUNTSVILLE	AL	35805	MADISON	USA	Food and Drug Administration Research	001	1	9/11/2014	NEW	$0
2014	2014	CFD RESEARCH CORPORATION	215 WYNN DR, 5TH FLOOR	HUNTSVILLE	AL	35805	MADISON	USA	Food and Drug Administration Research	000	1	9/10/2014	NEW	$148,122
														Subtotal = $148,122

Grand Total All Awards = $453,423

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An integrated multiscale-multiphysics modeling and simulation of ocular drug delivery with whole-body pharmacokinetic response

Award Number: U01FD005219

ORGANIZATION: FOOD AND DRUG ADMINISTRATION

OPDIV: FDA

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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