Topically Applied Steroids in Corneal Disease

Kupferman, Allan; Leibowitz, Howard M.

doi:10.1001/archopht.1974.03900060389009

Cited by 25 publications

(10 citation statements)

References 4 publications

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“…2 Many topically instilled drugs reach the internal segments of the eye through the cornea. 2 As stated by Dey et al (2003), 2 “these drugs include steroids, 31,32 ß-blockers, 33,34 antibiotics, 35,36,37 and nonsteroidal anti-inflammatory agents. 38 ” The cul-de-sac, as a route for topical drug administration, is the most common route of ocular drug delivery.…”

Section: Discussionmentioning

confidence: 99%

Molecular Expression and Functional Evidence of a Drug Efflux Pump (BCRP) in Human Corneal Epithelial Cells

Karla

Earla

Boddu

et al. 2009

Current Eye Research

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Purpose Breast Cancer Resistance Protein (BCRP) belongs to the family of efflux transporters involved in drug efflux leading to drug resistance. The objective of this study was to explore physical barriers for ocular drug absorption and to verify the presence and possible role of BCRP as a bar-rier for ocular drug resistance. Methods Transfected human corneal epithelial cells (SV40-HCEC) were selected as an in vitro model for corneal epithelium with MDCKII-BCRP as positive control. [3H]-Mitoxantrone ([3H]-MTX), which is a proven substrate for organic anion transporter like BCRP, was selected as a model drug for functional expression studies. Fumetremorgin C (FTC), a known specific inhibitor for BCRP and GF120918, an inhibitor for BCRP and P-gp, were added to inhibit BCRP-mediated efflux. PGP-4008, a specific inhibitor of P-gp was used to delineate the contribution of P-gp. The mRNA extracted from cells was used for RT-PCR analysis and gene expression. Membrane fractions of SV40-HCEC and MDCKII-BCRP were used for immunoprecipitation followed by Western blot analysis. Results Efflux was inhibited significantly in the presence of FTC and GF120918. Dose-dependent inhibition of efflux by BCRP was noticed in SV40-HCEC and MDCKII-BCRP in the presence of FTC and GF120918, and the efflux was ATP-dependent. The metabolic inhibitor, 2,4-DNP, significantly inhibited efflux. No pH-dependent efflux was noticed except at pH 5.5. RT-PCR analysis indicated a unique and distinct band at ~429 bp, corresponding to BCRP in SV40-HCEC and MDCKII-BCRP cells. Western Blot analysis indicated a specific band at ~70 kDa in the membrane fraction of SV40-HCEC and MDCKII-BCRP cells. Conclusions We have demonstrated the expression of BCRP in human corneal epithelial cells and, for the first time, demonstrated its functional activity leading to drug efflux. RT-PCR and Western blot analysis further confirmed this finding.

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Section: Discussionmentioning

confidence: 99%

Molecular Expression and Functional Evidence of a Drug Efflux Pump (BCRP) in Human Corneal Epithelial Cells

Karla

Earla

Boddu

et al. 2009

Current Eye Research

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“…It does not seem unreasonable to expect that a highly lipophilic steroid such as fluorometholone will tend to concentrate in the epithelial layer, perhaps even reaching a saturation concentration prior to passage through the hydrophilic layers of the cornea. Such a mechanism is not unlikely and was recently speculated upon for other steroidal compounds in a study using prednisolone acetate (9). In such a process, the rate and extent to which the epi-Vol.…”

Section: Effects Of Vehicle On Aqueous Humor Levels Of Fluo-mentioning

confidence: 95%

“…Whenever a true solution of a drug is administered to the eye, the ultimate aqueous humor drug concentration that may be attained is influenced by a number of controlling factors. These variables include the concentration of the drug in the vehicle (9,10,13), the volume of the instilled dose (14), the viscosity of the vehicle (15, 16), the influence of tear turnover and drainage on the instilled dose (14), and the absorption and elimination characteristics of the drug. For ophthalmic suspension systems, the additional parameters of intrinsic solubility and dissolution rate must be considered since the residence or contact time of the drug in the eye is usually brief.…”

Section: Introductionmentioning

confidence: 99%

“…These investigations have provided information regarding the intraocular penetration of dexamethasone (1)(2)(3)(4)(5)(6), prednisone (6-lo), prednisolone (6-lo), cortisone (11-13), hydrocortisone (11-13), and other related corticosteroids (12). Some studies have also included various derivatives of the parent compounds and have provided information pertaining to the influence of a drug's relative lipid and water solubilities on its ability to penetrate the epithelial layer of the cornea (5,6,9).…”

mentioning

confidence: 99%

“…In addition, the dosing systems used in these studies have been formulated to include aqueous solutions (2-4, lo), suspensions (1,(7)(8)(9)(11)(12)(13), and various ointment vehicles (4, 5,10). However, a mechanistic interpretation of the influence of these vehicles on the biological properties of the drug in ocular studies has not been explored in the literature.…”

mentioning

confidence: 99%

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