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Critical Reviews™ in Therapeutic Drug Carrier Systems

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ISSN Imprimir: 0743-4863

ISSN On-line: 2162-660X

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Enhancement of Ocular Drug Penetration

Volume 16, Edição 1, 1999, 62 pages
DOI: 10.1615/CritRevTherDrugCarrierSyst.v16.i1.20
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Hitoshi Sasaki
Department of Hospital Pharmacy, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Kenzo Yamamura
School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8131, Japan
Takahiro Mukai
School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8131, Japan
Koyo Nishida
School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8131, Japan
Junzo Nakamura
School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8131, Japan
Mikiro Nakashima
Department of Hospital Pharmacy, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Masataka Ichikawa
Department of Hospital Pharmacy, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan

RESUMO

Although new drugs have recently been developed within the field of ophthalmology, the eye's various defense mechanisms make it difficult to achieve an effective concentration of these drugs within the eye. Drugs administered systemically have poor access to the inside of the eye because of the blood-aqueous and blood-retinal barriers. And although topical instillation of drags is very popular in ophthalmology, topically applied drugs are rapidly eliminated from the precorneal area. In addition, the cornea, considered a major pathway for ocular penetration of topically applied drugs, is an effective barrier to drug penetration, since the corneal epithelium has annular tight junctions (zonula occludens), which completely surround and effectively seal the superficial epithelial cells. Various drug-delivery systems have been developed to increase the topical bioavailability of ophthalmic drags by enhancement of the ocular drag penetration. The first approach is to modify the physicochemical property of drags by chemical and pharmaceutical means. An optimum promoiety can be covalently bound to a drag molecule to obtain a prodrug that can chemically or enzymatically be converted to the active parent drag, either within the cornea or after the corneal penetration. Along these same lines, the transient formation of a lipophilic ion pair by ionic bonding is also useful for improving ocular drug penetration. The second approach is to modify the integrity of the corneal epithelium transiently by coadministration of an amphiphilic substance or by chelating agents that act as drug-penetration enhancers. The third approach modifies the integrity of the corneal epithelium transiendy by physical techniques including iontophoresis and phonophoresis. This paper reviews the absorption behavior and ocular membranes penetration of topically applied drags, and the various approaches for enhancement of ocular drug penetration in the eye.

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