Physical and theoretical models of vascular and anatomical systems are being used in our laboratory to study a variety of phenomena such as the distribution of anti-HIV drugs, hemodynamic effects in vascular disease, and transport of drugs into visceral tissues and the eye. Several projects have been emphasized this past year. (1) We have developed a physiologic pharmacokinetic model of the distribution of a pro-drug, F-ddA, for treating HIV infection in the central nervous system of AIDS patients. The model will guide the design of more effective drugs that will be better absorbed in the gastrointestinal tract after oral doses, and will also penetrate adequately into the brain and cerebral spinal fluid. (2) We are studying the interrelationship between blood flow patterns and the mass transport of macromolecules into the arterial wall as a possible explanation of lesion site preferences associated with atherosclerosis. We have fabricated a mechanical model of a branching flow system that is made of semi-permeable wall material to study convection / diffusion through the wall. We are theoretically simulating flow and transport in model arteries to corroborate our experiments. (3) Selective delivery of therapeutic agents to targeted hepatobiliary and renal tissues would make possible safer, more effective treatments by optimizing doses and reducing systemic toxicity. We are developing an infusion system for delivering drugs and gene vectors to the liver, gall bladder and urinary bladder under well-controlled and monitored conditions of pressure and flow. Pharmacokinetic studies will be performed, and infusate distribution will be measured in blood, liver and bladder. (4) A number of inflammatory and neoplastic diseases of the eye are now treated by repeated intravitreal drug injection. We are developing sustained drug release devices for intravitreal implantation that could release drugs for periods as long as five years. These would eliminate the need for frequent invasive intervention. A number of different drugs and device configurations are being evaluated. Mathematical models that incorporate the geometry and physical properties of the device, physico-chemical properties of the drug, and physiology of the eye are being developed to assist in design of the devices. (This is a continuation of Intramural Research Project Z01-RR- 10324-09 BEI.) - pharmacokinetic models, hemodynamics, regional drug delivery, sustained drug release

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Intramural Research (Z01)
Project #
1Z01OD010324-02
Application #
6290684
Study Section
Special Emphasis Panel (BE)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Office of the Director, National Institutes of Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Robinson, Michael R; Lee, Susan S; Kim, Hyuncheol et al. (2006) A rabbit model for assessing the ocular barriers to the transscleral delivery of triamcinolone acetonide. Exp Eye Res 82:479-87
Kim, Hyuncheol; Csaky, Karl G; Gravlin, Luisa et al. (2006) Safety and pharmacokinetics of a preservative-free triamcinolone acetonide formulation for intravitreal administration. Retina 26:523-30
Kim, Hyuncheol; Csaky, Karl G; Chan, Chi-Chao et al. (2006) The pharmacokinetics of rituximab following an intravitreal injection. Exp Eye Res 82:760-6
Kim, Hyuncheol; Csaky, Karl G; Gilger, Brian C et al. (2005) Preclinical evaluation of a novel episcleral cyclosporine implant for ocular graft-versus-host disease. Invest Ophthalmol Vis Sci 46:655-62
Kim, Hyuncheol; Lizak, Martin J; Tansey, Ginger et al. (2005) Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging. Ann Biomed Eng 33:150-64
Amaral, Juan; Fariss, Robert N; Campos, Maria M et al. (2005) Transscleral-RPE permeability of PEDF and ovalbumin proteins: implications for subconjunctival protein delivery. Invest Ophthalmol Vis Sci 46:4383-92
Park, Juyoung; Bungay, Peter M; Lutz, Robert J et al. (2005) Evaluation of coupled convective-diffusive transport of drugs administered by intravitreal injection and controlled release implant. J Control Release 105:279-95
Kim, Hyuncheol; Robinson, Michael R; Lizak, Martin J et al. (2004) Controlled drug release from an ocular implant: an evaluation using dynamic three-dimensional magnetic resonance imaging. Invest Ophthalmol Vis Sci 45:2722-31
Yim, Peter J; Cebral, Juan R; Weaver, Ashley et al. (2004) Estimation of the differential pressure at renal artery stenoses. Magn Reson Med 51:969-77
Lutz, Robert J; Warren, Kathy; Balis, Frank et al. (2002) Mixing during intravertebral arterial infusions in an in vitro model. J Neurooncol 58:95-106

Showing the most recent 10 out of 12 publications