Ciliary Muscle Capillaries Have Blood–Tissue Barrier Characteristics

Schlingemann, Reinier O.; Hofman, P; Klooster, Jan; Blaauwgeers, Hans; Gaag, R van der; Vrensen, Gijs F.J.M.

doi:10.1006/exer.1998.0483

Cited by 38 publications

(14 citation statements)

References 21 publications

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“…5,28 The expression of P-gp has also been detected in human and rat iridial capillaries and cultured bovine ciliary nonpigmented epithelial cells. 29,30 Verapamil and quinidine are substrates of P-gp. 31 It is also most likely a substrate of an unclear cationic transporter that carries out efflux transportation at the outer BRB.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Drug Permeabilities Across the Blood–Retinal Barrier, Blood–Aqueous Humor Barrier, and Blood–Brain Barrier

Toda

Kawazu

Oyabu

et al. 2011

Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 99%

Comparison of Drug Permeabilities Across the Blood–Retinal Barrier, Blood–Aqueous Humor Barrier, and Blood–Brain Barrier

Toda

Kawazu

Oyabu

et al. 2011

Journal of Pharmaceutical Sciences

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“…In the eye, P-gp is expressed in the retinal capillary endothelial cells (Holash and Stewart, 1993), retinal pigmented epithelial cells (Schlingemann et al, 1998), ciliary nonpigmented epithelium (Wu et al, 1996), conjunctival epithelial cells (Saha et al, 1998), and iris and ciliary muscle cells (Holash and Stewart, 1993). More recently, P-gp has been identified in the human and rabbit cornea for the first time in our laboratory (Dey et al, 2003).…”

mentioning

confidence: 84%

Pharmacokinetics of Erythromycin in Rabbit Corneas after Single-Dose Infusion: Role of P-Glycoprotein as a Barrier to in Vivo Ocular Drug Absorption

Dey

Gunda²,

Mitra³

2004

J Pharmacol Exp Ther

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Efflux pump like P-glycoprotein (P-gp) is known to be a major barrier to drug delivery. Functional P-glycoprotein has been recently identified in cornea and corneal cell lines. Thus, it is probable that P-glycoprotein may restrict in vivo ocular drug absorption, resulting in low ocular bioavailability. Experiments were designed using New Zealand albino (New Zealand White) rabbits to assess inhibitors of P-gp efflux to increase drug absorption. Anesthetized rabbits were given constant topical infusions of [14 C]erythromycin in the presence and absence of inhibitors. Testosterone, verapamil, quinidine, and cyclosporine A were selected as P-gp inhibitors. Transport experiments were conducted in Madin-Darby canine kidney cells transfected with the human mdr1 gene (MDCK-MDR1). Erythromycin exhibited significant efflux out of MDCK-MDR1 cells, suggesting that erythromycin is a good substrate for P-gp. Ocular pharmacokinetic studies were conducted using a topical single-dose infusion method. Maximum inhibition of P-gp mediated efflux was observed with 500 M testosterone. Area under the curve (AUC) 0-ϱ of erythromycin with 500 M testosterone was almost 4 times higher than AUC 0-ϱ without any inhibitor. Rate of elimination (k 10 ) for erythromycin and those with inhibitors was found to be similar (141 Ϯ 23 min), suggesting that elimination pathways were not altered. All the inhibitors were found to be nontoxic. Verapamil also inhibited the efflux pump with moderate change in AUC 0-ϱ and C max compared with control. Thus, P-gp is found to be active in vivo, and it restricts topical erythromycin absorption across the cornea, which can be inhibited by known P-gp inhibitors. Therefore, ocular bioavailability of P-gp substrates can be significantly enhanced by proper selection of P-gp inhibitors.

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“…However, the barrier functionality of BAB is not complete even when it is intact [60] . Injected horse radish peroxidase (HRP; 40 kDa) was shown to reach the aqueous humor through the fenestrated capillaries of the ciliary but not via the iris blood vessels, which control the permeation of plasma proteins into the aqueous humor [61] .…”

Section: Blood-aqueous Barriermentioning

confidence: 99%

Ocular novel drug delivery: impacts of membranes and barriers

Barar

Javadzadeh

Omidi

2008

Expert Opinion on Drug Delivery

272

116

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Background : Ocular drug delivery is an extremely challenging area due to its restrictive barrier functionalities. Objective : Drug transport via corneal/non-corneal routes involves several intricate biological processes such as drug penetration across the ocular barriers and transfer to the anterior or posterior chambers, thus the influence of these processes on the pharmacotherapy of the eye should be fully addressed. Methods : To pursue the impacts of such impediments in novel drug therapy, recent publications were reviewed regarding advanced strategies such as nanomedicines. Conclusion : The ocular barriers are highly specialized and selectively control the inward/outward traverse of compounds, hence a better understanding of these biological obstacles would provide a platform to advance ophthalmic drug therapy towards specified delivery/targeting with minimal adverse consequences.

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Ciliary Muscle Capillaries Have Blood–Tissue Barrier Characteristics

Cited by 38 publications

References 21 publications

Comparison of Drug Permeabilities Across the Blood–Retinal Barrier, Blood–Aqueous Humor Barrier, and Blood–Brain Barrier

Comparison of Drug Permeabilities Across the Blood–Retinal Barrier, Blood–Aqueous Humor Barrier, and Blood–Brain Barrier

Pharmacokinetics of Erythromycin in Rabbit Corneas after Single-Dose Infusion: Role of P-Glycoprotein as a Barrier to in Vivo Ocular Drug Absorption

Ocular novel drug delivery: impacts of membranes and barriers

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