The existing methods to treat posterior eye diseases are intravitreal and periocular injections or systemic drug administration. Posterior eye diseases such as posterior uveitis, endophthalmitis, and age-related macular degeneration affect more than a million people in the United States each year. Systemic administration for the treatments of posterior eye diseases is usually not preferred because of the systemic toxicity encountered. Intravitreal and periocular injections are more effective routes of administration to treat posterior eye diseases compared with systemic drug delivery, but repeated injections cause side effects such as pain, intraocular bleeding, increased chances for infection, and the possibility of retinal detachment. Ocular injections also involve high health care cost because of the participation of experienced ophthalmologists in carrying out the treatments. An effective low-cost robust non-invasive drug delivery system for the treatments of posterior eye diseases has yet to be developed. There is also a lack of human pharmacokinetic data of ocular drug delivery in general. Ocular iontophoresis is a noninvasive method and has potential for drug delivery to the posterior of the eye. However, the mechanisms of ocular iontophoresis are not well understood, and there is much room for significant improvement of ocular iontophoretic drug delivery from the standpoint of the physical chemistry of ion transport and engineering. Also, the development of a non-invasive approach to study ocular drug pharmacokinetics in the posterior of the eye will be beneficial in ocular drug delivery research. The main objectives of the present project are (a) to characterize the transport properties of ocular iontophoresis and develop a more effective iontophoresis method for the treatment of posterior eye disease and (b) to develop magnetic resonance imaging (MRI) for ocular pharmacokinetic studies and perform these studies following ocular drug delivery such as iontophoresis. The project will be led by scientists in pharmaceutics and pharmaceutical chemistry (S.K. Li, College of Pharmacy, University of Utah), physics and radiology (E-K. Jeong, Utah Center for Advanced Imaging Research) and ophthalmology (P.S. Bernstein, Moran Eye Center). The information obtained in the present proposal will provide a knowledge base that allows pharmaceutical scientists to improve ocular iontophoresis and other drug delivery systems. It will be a great benefit to the public if an effective drug delivery system such as ocular iontophoresis can replace injections and systemic administration for drug delivery to the back of the eye.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY015181-05S1
Application #
8005882
Study Section
Special Emphasis Panel (ZRG1-BST-A (50))
Program Officer
Mariani, Andrew P
Project Start
2005-09-15
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2012-01-31
Support Year
5
Fiscal Year
2010
Total Cost
$73,337
Indirect Cost
Name
University of Cincinnati
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Wen, He; Hao, Jinsong; Li, S Kevin (2013) Characterization of human sclera barrier properties for transscleral delivery of bevacizumab and ranibizumab. J Pharm Sci 102:892-903
Chopra, Poonam; Hao, Jinsong; Li, S Kevin (2013) Influence of drug lipophilicity on drug release from sclera after iontophoretic delivery of mixed micellar carrier system to human sclera. J Pharm Sci 102:480-8
Chopra, Poonam; Hao, Jinsong; Li, S Kevin (2012) Sustained release micellar carrier systems for iontophoretic transport of dexamethasone across human sclera. J Control Release 160:96-104
Li, S Kevin; Hao, Jinsong; Liu, Hongshan et al. (2012) MRI study of subconjunctival and intravitreal injections. J Pharm Sci 101:2353-63
Hao, Jinsong; Yang, Michael B; Liu, Hongzhuo et al. (2011) Distribution of propranolol in periocular tissues: a comparison of topical and systemic administration. J Ocul Pharmacol Ther 27:453-9
Li, S Kevin; Liddell, Mark R; Wen, He (2011) Effective electrophoretic mobilities and charges of anti-VEGF proteins determined by capillary zone electrophoresis. J Pharm Biomed Anal 55:603-7
Jeong, Eun-Kee; Sung, Young-Hoon; Kim, Seong-Eun et al. (2011) Measurement of creatine kinase reaction rate in human brain using magnetization transfer image-selected in vivo spectroscopy (MT-ISIS) and a volume ³¹P/¹H radiofrequency coil in a clinical 3-T MRI system. NMR Biomed 24:765-70
Shi, Xianfeng; Liu, Xin; Wu, Xueming et al. (2011) Ocular pharmacokinetic study using Týýý mapping and Gd-chelate- labeled polymers. Pharm Res 28:3180-8
Liu, Xin; Feng, Yi; Lu, Zheng-Rong et al. (2010) Rapid simultaneous acquisition of T1 and T2 mapping images using multishot double spin-echo EPI and automated variations of TR and TE (ms-DSEPI-T12). NMR Biomed 23:97-104
Wen, He; Hao, Jinsong; Li, S Kevin (2010) Influence of permeant lipophilicity on permeation across human sclera. Pharm Res 27:2446-56

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