Model for Porosity Changes Occurring during Ultrasound-Enhanced Transcorneal Drug Delivery.
Ultrasound-enhanced drug delivery through the cornea has considerable therapeutic potential. However, our understanding of how ultrasound enhances drug transport is poor, as is our ability to predict the increased level of transport for given ultrasound parameters. Described here is a computational model for quantifying changes in corneal porosity during ultrasound exposure. The model is calibrated through experiments involving sodium fluorescein transport through rabbit cornea. Validation was performed using nylon filters, for which the properties are known. It was found that exposure to 800-kHz ultrasound at an intensity 2 W/cm2for 5 min increased the porosity of the epithelium by a factor of 5. The model can be useful for determining the extent to which ultrasound enhances the amount of drug transported through biological barriers, and the time at which a therapeutic dose is achieved at a given location, for different drugs and exposure strategies.
Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland, USA.
Prasanna
P
Hariharan
Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland, USA.
Marjan
M
Nabili
Department of Biomedical Engineering, The George Washington University, Washington, DC, USA.
Allan
A
Guan
Department of Biomedical Engineering, The George Washington University, Washington, DC, USA.
Vesna
V
Zderic
Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland, USA. Electronic address: matthew.myers@fda.hhs.gov.
Matthew
M
Myers
D060433:Administration, Ophthalmic; D003198:Computer Simulation; D003315:Cornea / Q000737:chemistry* / Q000528:radiation effects*; D004058:Diffusion; D018274:Electroporation / Q000379:methods*; D019220:High-Energy Shock Waves; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D016062:Porosity / Q000528:radiation effects*; D011829:Radiation Dosage; D013010:Sonication / Q000379:methods*
D004364:Pharmaceutical Preparations
Drug delivery; Ocular; Porous medium model; Ultrasound