Drug transport ocular

Barriers to Drug Transport in Ocular Epithelia Uday B. Kompella and Vincent H. L. Lee... 

JA Zadunaisky, B Spinowitz. (1977). Drugs affecting the transport and permeability of the corneal epithelium. In S Dikstein, ed. Drugs and Ocular Tissues. Basel Krager, pp 57-78. 

J. J. Yang, H. Ueda, K. Kim, and V. H. Lee. Meeting future challenges in topical ocular drug delivery Development of an air-interfaced primary culture of rabbit conjunctival epithelial cells on a permeable support for drug transport studies. J Control Release 65 1-11 (2000). 

For in vitro toxicity studies and assessment of the barrier function, drug transport, cell physiology, and metabolism as well as the development of delivery systems, cell culture models provide powerful systems for scientific research. As the corneal epithelium is the main barrier for ocular penetration, various corneal epithelial cell cultures were established besides the corneal constructs that mimic the whole cornea and serve as reductionist models for the ocular barrier. In general, two types of cell culture models are available primary cell cultures and immortalized, continuous cell lines. 

Even though we are currently far from having penetration enhancers that fulfill all or most of the above requirements, several classes of ocular absorption enhancers, however, are being evaluated for their suitability under the conditions of use by various groups. This chapter aims to discuss various classes of ocular absorption enhancers, along with the basic modes of drug transport and the mechanism by which these penetration enhancers act. Further, new categories of penetration enhancers, which have been reported more recently, are also included. 

In addition to the corneal route, topically applied ocular drugs may be absorbed via a noncorneal absorption route that involves drug transport across the bulbar conjunctiva and underlying sclera into the uveal tract and vitreous humor.65 The intercellular spaces of the conjunctival epithelium are wider than those of the corneal epithelium. As a result, the conjunctiva has higher permeability than the cornea to agents such as mannitol, inulin, and FITC-dextran.86 The penetration of peptides, however, is limited by enzymatic degradation.87 The limit of molecular size for conjunctival penetration is between 20,000 and 40,000 Da. Vitreous can act as an aqueous and unstirred diffusion barrier to drug permeation.64... 

Penetration Enhancers The transport process across the corneal tissue is the rate-limiting step in ocular drug absorption. Increasing the permeability of the corneal epithelium by penetration enhancers is likely to enhance the drug transport across the corneal tissues and therefore improve ocular bioavailability of the drug. 

OCULAR DRUG TRANSPORT AND DELIVERY Modes of Transport... 

Mannermaa, E. Vellonen, K.S. Urtti, A. Drug transport in corneal epithelium and blood-retina barrier Emerging role of transporters in ocular pharmacokinetics. Adv. Drug Deliv. Rev. 2006, 58 (11), 1136-1163. 

Evaporation of the tear film from the precorneal area can cause changes in the concentration of instilled drug solutions, and therefore can affect the rate of drug transport across the ocular membranes. 

Robinson, J.R. Ocular drug delivery mechanism(s) of corneal drug transport and mucoad-hesive delivery systems. STP. Pharm. Sci. 5(12), 839-846 (1989)... 

The significance of the barrier function of membranes has been the topic of considerable research. The blood-brain barrier and the blood-retinal barrier are well understood, and the microscopic structures imparting and controlling barrier properties have been quite thoroughly investigated and the science reviewed [15, 154-155], The structures and functions of ocular membranes specific to transport associated with ophthalmic drug administration also have been topics of extensive research [15, 157-158],... 

In order to design such an efficient and effective device, one must understand the mechanisms by which drug is transported in the ocular interior. One issue debated in the literature for some time has been the relative importance of transport by passive diffusion versus that facilitated by the flow of fluid in the vitreous (see, e.g., Ref. 226). To predict the geometric distribution even at steady state of drug released from an implant or an intravitreal injection, one must appreciate which of these mechanisms is at work or, as appropriate, their relative balance. 

Keywords Ocular drug delivery Noncorneal route Transporters Iontophoresis Endocytosis Dry eye Inflammation Subconjunctival injections... 

K. Hosoya, V. H. Lee, and K. J. Kim. Roles of the conjunctiva in ocular drug delivery a review of conjunctival transport mechanisms and their regulation. Eur J Pharm Biopharm 60 227-240 (2005)... 

The experimental methods for evaluating the BRB transport in vivo and the ocular pharmacokinetics of systemic drug administration are relatively straightforward and have been in use for over two decades. Overall, they are useful as a guide for the selection of drug candidates for the treatment of retinal diseases. With the combined use of conventional in vivo methods and newly developed... 

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