<i>In vitro</i>cell culture models to study the corneal drug absorption

Reichl, Stephan; Kölln, Christian; Hahne, M.; Verstraelen, Jessica

doi:10.1517/17425255.2011.562195

Cited by 43 publications

(20 citation statements)

References 129 publications

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“…It consists of five different layers, namely epithelium, Bowman’s membrane, stroma, Descemet’s membrane, and endothelium. The corneal epithelium plays a major role in limiting trans-corneal drug absorption with a drug permeability rate of only 10 −7 -10 −5 cm s −1 [24]. While small lipophilic drugs are passively transported via the transcellular pathway, hydrophilic drugs undergo restricted permeation through tight junctions via the paracellular pathway.…”

Section: Challenges To Ocular Drug Deliverymentioning

confidence: 99%

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies

Mandal

Bisht

Rupenthal

2017

Journal of Controlled Release

384

185

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Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies.

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Section: Challenges To Ocular Drug Deliverymentioning

confidence: 99%

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies

Mandal

Bisht

Rupenthal

2017

Journal of Controlled Release

384

185

View full text Add to dashboard Cite

show abstract

“…Thus, using an in vitro corneal epithelial model will allow replication of the relevant factors of the in vivo environment. Human corneal in vitro models offer a cost effective and more standardizable substitutes [36] for animal studies while allowing a higher throughput testing of biomaterial interaction and drug permeation [37]. Reconstructed corneal equivalents as well as cell culture models of the corneal epithelium have been successfully used to study ocular toxicity and permeability [37]–[41].…”

Section: Introductionmentioning

confidence: 99%

Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

2014

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In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

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“…Transepithelial electrical resistance (TEER) has been shown to be a valid and reliable method for measurement of the functional integrity of the epithelial barrier (Hasegawa et al, 1999; Hashimoto et al, 2008; Meyer et al, 2001; Reichl et al, 2011). TEER in whole-mount tissue specimen of ovine, porcine, and rabbit vocal fold has been studied ex vivo in Ussing chambers (Alper et al, 2011; Kojima et al, 2014a; Sivasankar and Fisher, 2008, 2007).…”

Section: Introductionmentioning

confidence: 99%

Structurally and functionally characterized in vitro model of rabbit vocal fold epithelium

et al. 2017

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In this paper, we describe a method for primary culture of a well-differentiated electrically tight rabbit vocal fold epithelial cell multilayer and the measurement of transepithelial electrical resistance (TEER) for the evaluation of epithelial barrier function in vitro. Rabbit larynges were harvested and enzymatically treated to isolate vocal fold epithelial cells and to establish primary culture. Vocal fold epithelial cells were co-cultured with mitomycin C-treated feeder cells on collagen-coated plates. After 10–14 days in primary culture, cells were passaged and cultured until they achieved 70–90% confluence on collagen-coated plates. Epithelial cells were then passaged onto collagen-coated cell culture inserts using 4.5 cm2 membrane filters (1.0 μm pore size) with 10% fetal bovine serum or 30 μg/mL bovine pituitary extract to investigate the effects of growth-promoting additives on TEER. Additional experiments were performed to investigate optimal seeding density (1.1, 2.2, 4.4, or 8.9 × 105 cells/cm2), the effect of co-culture with feeder cells, and the effect of passage number on epithelial barrier function. Characterization of in vitro cultures was performed using hematoxylin and eosin staining and immunostaining for vocal fold epithelial cell markers and tight junctions. Results revealed higher TEER in cells supplemented with fetal bovine serum compared to bovine pituitary extract. TEER was highest in cells passaged at a seeding density of 2.2 × 104 cells/cm2, and TEER was higher in cells at passage two than passage three. Ultrastructural experiments revealed a well-differentiated epithelial cell multilayer, expressing the epithelial cell markers CK13, CK14 and the tight junction proteins occludin and ZO-1.

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In vitrocell culture models to study the corneal drug absorption

Abstract: Current human 3D corneal cell culture models have the potential to replace excised animal corneas in drug absorption studies. However, for widespread use, the contemporary validation of existent systems is required.

Cited by 43 publications

References 129 publications

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies

Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

Structurally and functionally characterized in vitro model of rabbit vocal fold epithelium

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