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The human nail, like any biological material, is not readily available in large amounts and shows some variability from one individual to another. Replacing it by synthetic models is of great interest to perform reproducible and reliable tests in order to assess drug diffusion or nail lacquer adhesion for example. Keratin films, produced at the lab scale from natural hair, and the commercially available Vitro-nail® sheets have been proposed as models of human nails. In this study, we have investigated in detail these two materials. Surface aspect, composition, surface energy and water permeation were determined by SEM-EDS, ATR-FTIR, XPS, DVS and tensiometry and were compared to those of nails clippings. The development of a probe tack test using a rotational rheometer allowed us to measure the adhesion of three different nail lacquers on each substrate and the results were correlated with the surface state. It is shown that except roughness, keratin films exhibit similar composition, water sorption and surface energy as human nails. Vitro-nail® presents a more hydrophilic and permeable behavior than natural nail due to probable higher proportions of amide functions and absence of disulfide bridges. With the aim to improve nail lacquer residence, the importance of adsorption, electrostatic and mechanical adhesions as well as water sorption behavior is highlighted and allowed to show the importance of roughness, a low surface energy, a moderate hydrophobicity and an ability to form hydrogen and electrostatic bonds in order to optimize adhesion., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present overview deals with current approaches for the improvement of in vitro models for preclinical drug and formulation screening which were elaborated in a joint project at the Center of Pharmaceutical Engineering of the TU Braunschweig. Within this project a special focus was laid on the enhancement of skin and cornea models. For this reason, first, a computation-based approach for in silico modeling of dermal cell proliferation and differentiation was developed. The simulation should for example enhance the understanding of the performed 2D in vitro tests on the antiproliferative effect of hyperforin. A second approach aimed at establishing in vivo-like dynamic conditions in in vitro drug absorption studies in contrast to the commonly used static conditions. The reported Dynamic Micro Tissue Engineering System (DynaMiTES) combines the advantages of in vitro cell culture models and microfluidic systems for the emulation of dynamic drug absorption at different physiological barriers and, later, for the investigation of dynamic culture conditions. Finally, cryopreserved shipping was investigated for a human hemicornea construct. As the implementation of a tissue-engineering laboratory is time-consuming and cost-intensive, commercial availability of advanced 3D human tissue is preferred from a variety of companies. However, for shipping purposes cryopreservation is a challenge to maintain the same quality and performance of the tissue in the laboratory of both, the provider and the customer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The most extensively characterized human-derived cell line used in transcorneal permeability studies, in terms of passive transcellular and paracellular transport, transporter expression and metabolic enzymes, is the immortalized human corneal epithelial cell line (HCE-T). The purpose of this study is to describe the changes in the HCE-T barrier phenotype in vitro when valid cultivation conditions, in accordance with the standardized HCE-T cell-based model protocol, were employed. Evaluation of the structural and functional barrier properties revealed two different HCE-T barrier phenotypes, depending on the polycarbonate membrane pore size. Model I (pore size 0.4μm) was characterized by a multilayered HCE-T epithelium at the apical side and a weak barrier function (70-115Ω×cm 2 ), whereas Model II (pore size 3μm) consisted of an apical lipophilic HCE-T monolayer and a basolateral lipophilic monolayer of migrated HCE-T cells that showed improved barrier properties (1700-2600Ω×cm 2 ) compared with Model I. Considering the permeation of ophthalmic compounds and in vitro/ex vivo correlation, Model II was better able to predict transcorneal drug permeation. This study highlights the important aspects of HCE-T barrier phenotype variability that should be continuously monitored in the routine application of HCE-T cell-based models across both academic and pharmaceutical industry research laboratories., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The development and registration of reformulated ophthalmic products (OPs) requires eye-related bioavailability (BA) assessments. Common BA algorithms associated with other routes of application, such as the oral route, cannot be easily applied to eye-related BA testing. Here, we provide an analysis of the current literature and suggestions for further directions in the development of high-capacity, cost-effective, and highly predictive nonclinical models of eye-related drug BA. One, or a combination of these models, has the potential for routine use in research laboratories and/or the pharmaceutical industry to overcome various obstacles in reformulated OP development and registration., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The kinetics of drug absorption for nasally administered drugs are often studied using excised mucosal tissue. To avoid the disadvantages of animal experiments, cellular in-vitro models have been established. This study describes the optimization of culture conditions for a model based on the RPMI 2650 cell line, and an evaluation of this model's value for drug absorption studies., Methods: The cells were cultured in two serum-free media, serum-reduced variants or minimum essential medium (MEM) containing 5-20% serum. Cell seeding efficiency and proliferation behavior were evaluated in addition to viability and attachment following cryopreservation and thawing. Cells were cultured on different filter inserts for varying cultivation times. The epithelial barrier properties were determined by measuring transepithelial electrical resistance (TEER). Permeability was assessed using marker substances., Key Findings: Serum supplementation of medium was necessary for cultivation, whereas the serum concentration showed little impact on proliferation and attachment following cryopreservation. A pronounced dependence of TEER on medium and filter material was observed. An optimized model cultured with MEM containing 10% serum on polyethylene terephthalate exhibited permeability that was similar to excised nasal mucosa., Conclusions: These data indicate that this model could be an appropriate alternative to excised mucosa for the in-vitro evaluation of nasal drug absorption., (© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.)

Introduction: Many diseases of the anterior eye segment are treated using topically applied ophthalmic drugs. For these drugs, the cornea is the main barrier to reaching the interior of the eye. In vitro studies regarding transcorneal drug absorption are commonly performed using excised corneas from experimental animals. Due to several disadvantages and limitations of these animal experiments, establishing corneal cell culture models has been attempted as an alternative., Areas Covered: This review summarizes the development of in vitro models based on corneal cell cultures for permeation studies during the last 20 years, starting with simple epithelial models and moving toward complex organotypical 3D corneal equivalents., Expert Opinion: 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.

Cell culture models of the cornea are continually developed to replace the isolated animal cornea for transcorneal drug absorption studies. The aim of this study was to determine and compare epithelial tightness and permeability of currently available corneal cell culture models to avoid interlaboratory variability and to assess their usefulness for in-vitro permeation studies. Pure epithelial cell culture models (CEPI, SIRC and HCE-T cell lines), primary cultures of human corneal epithelium (HCEpiC) and the two commercially available models (RHC and Epiocular), as well as organotypic human cornea constructs (HCC, HCC-HCE-T), were investigated and data were compared with those obtained from the excised bovine cornea. Barrier properties were assessed by measurements of transepithelial electrical resistance (TEER) and permeability of three passively absorbed substances (mannitol, testosterone and timolol maleate) with different physico-chemical properties. TEER experiments revealed weak barrier functions for all of the investigated epithelial models (