Phospholipid Vesicle-Based Permeation Assay and EpiSkin® in Assessment of Drug Therapies Destined for Skin Administration

Abstract

Cost-effective and efficient methods for permeability screening are crucial during early development of drugs, drug formulations, and cosmeceuticals. Alternatives to animal experiments are impelled for both economical and ethical reasons. The aim of this study was to determine the ability of the phospholipid vesicle-based permeation assay (PVPA) to assess the effect of different formulations on drug permeability and thus establish its utility in formulation development. Three model drugs were tested in solutions and as liposomal formulations. The permeability results for the PVPA models were compared with the results for the reconstructed human skin model, EpiSkin(®). The drugs were ranked based on their estimated penetration potentials, and the results were in accordance with what was expected considering the physicochemical properties of the drugs. PVPAs (E-80, ceramide, cholesterol, cholesteryl sulfate, and palmitic acid) was able to distinguish between drug solutions and liposomal formulations; however, EpiSkin(®) detected only small differences between the drugs in solution and formulations. In contrast with EpiSkin(®), which is limited by a 3-day testing window, PVPA barriers can be stored frozen for up to 2 weeks or even up to 16 months, depending on their compositions. The PVPA models are thus more cost effective and efficient than the EpiSkin(®) model for permeability screening during early drug development.

Biomimetic PVPA in vitro model for estimation of the intestinal drug permeability using fasted and fed state simulated intestinal fluids

“…This effect has also been observed for the Chol containing PVPA mimicking stratum corneum (Engesland et al, 2014). Additional studies with other markers and drugs to further elucidate the barrier stability should be performed to enable a prolonged time period of use after the original barrier preparation.…”

“…Table 1 provides the composition of the different media and Table 2 gives an overview of the physicochemical and biopharmaceutical properties of employed model drugs and the marker calcein. Calcein was, based on experience from previous studies, chosen as a sensitive marker to detect any changes in barrier integrity (Engesland et al, 2014;Engesland et al, 2013;Fischer et al, 2011;Flaten et al, 2009;Flaten et al, 2006a;Flaten et al, 2006b;Flaten et al, 2008;Flaten et al, 2007;Naderkhani et al, 2014). The model drugs acyclovir (3 mM), griseofulvin (0.05 mM), indomethacin (0.3 mM) and nadolol (6 mM) were dissolved in concentrations that were high enough to facilitate reliable analyses of the samples from the acceptor compartments, but still well below the saturation limits.…”

FoxO1 enhances differentiation and apoptosis in human primary keratinocytes

“…Reconstructed human epidermis such as EpiSkin has been proposed to study skin permeability, irritancy, corrosiveness and phototoxicity . Aside from its histological structure and cell morphology akin to native epidermis, RHE can also express markers of epidermal proliferation and differentiation .…”

Successful co-encapsulation of benzoyl peroxide and chloramphenicol in liposomes by a novel manufacturing method - dual asymmetric centrifugation

“…i.e. CAM-encapsulation values of 32.5 ± 2.8 μg/mg was obtained for filter extruded liposomes (Engesland et al, 2015), although the authors prepared larger liposomes of around 670 nm in diameter. Also, previous studies in our group found that the encapsulation efficiency of approximately 30% (drug:lipid ratio = 31.12 ± 0.15 μg/mg) was achievable for CAM-liposomes prepared by probe sonication (Ingebrigtsen et al, 2016).…”