Development and Evaluation of a Human Skin Equivalent in a Semiautomatic Microfluidic Diffusion Chamber

There is an increasing demand for transdermal transport measurements to optimize topical drug formulations and to achieve proper penetration profile of cosmetic ingredients. Reflecting ethical concerns the use of both human and animal tissues is becoming more restricted. Therefore, the focus of dermal research is shifting towards in vitro assays. In the current proof-of-concept study a three-layer skin equivalent using human HaCaT keratinocytes, an electrospun polycaprolactone mesh and a collagen-I gel was compared to human excised skin samples. We measured the permeability of the samples for 2% caffeine cream using a miniaturized dynamic diffusion cell (“skin-on-a-chip” microfluidic device). Caffeine delivery exhibits similar transport kinetics through the artificial skin and the human tissue: after a rapid rise, a long-lasting high concentration steady state develops. This is markedly distinct from the kinetics measured when using cell-free constructs, where a shorter release was observable. These results imply that both the established skin equivalent and the microfluidic diffusion chamber can serve as a suitable base for further development of more complex tissue substitutes.

Transdermal Transport In Vitro of Domperidone by Compartmental Modeling Approach

Transdermal delivery can be alternatively chosen for domperidone to improve its low oral bioavailability. Development drugs into transdermal formulation need information about the transport mechanism of the drug. The purpose of this study was to develop models of domperidone transdermal transport in vitro based on compartmental modeling for understanding the domperidone transport mechanism. Domperidone solution (0,5 g/L in a citric buffer, pH 5) was filled into the donor compartment. The comparative study also conducted to examine the effect of different pH on domperidone transdermal transport in pH 1 (4g/L in 0,1 M HCl). The shed snake-skin and cellophane membrane were pretreated for 1 hour with chemical enhancers (oleic acid in propylene glycol) and assembled between the donor and the receptor compartment of the vertical diffusion cell. The receptor compartment was filled in with phosphate-buffered saline at a pH of 6.8. The permeation study was performed for 8 hours. Samples concentration was assayed by the UV-Spectrophotometry method. The cumulative permeation profiles of domperidone were analyzed using WinSAAM. Three and four-compartmental models were proposed with the one lag compartment. The evaluation of the appropriate number of compartments in the transport model was examined based on the visual goodness of fit (GOF) and the Corrected Akaike’s Information Criterion (AICc) values. Four-compartmental models with one lag compartment were the best model describing percutaneous domperidone transport either in pH donor of 5 or pH 1. The model indicates domperidone transport follows into two parallel routes, including a lag compartment.

Tuning the Transdermal Transport by Application of External Continuous Electric Field: A Molecular Dynamics Coarse-Grained Study.

The control of skin permeability to specific substances (e.g., drugs, vitamins, nutrients) have been prosecuted for a long time. Electroporation and iontophoresis are techniques that enable the transport of substances...

Safe therapy of osteoarthritis: place of topical nonsteroidal anti-inflammatory drugs

The article discusses the social significance of osteoarthritis as a widespread disease that develops mainly in older people, which makes it difficult to carry out anti-inflammatory and analgesic therapy due to the frequent combination of osteoarthritis with other diseases at this age, the need to treat comorbid conditions, which is often poorly combined with systemic therapy with non-steroidal anti-inflammatory drugs. It is noted that osteoarthritis not only worsens the quality of life of patients, but also leads to a decrease in the length of their life, which emphasizes the medical and social importance of conducting the safest possible therapy for this disease. Data on the negative impact of the presence of chronic pain on the progression of osteoarthritis are presented. The negative aspects of the use of oral forms of non-steroidal anti-inflammatory drugs are discussed: the development of adverse events primarily from the gastrointestinal tract and cardiovascular system, the negative effect on the synthesis of glycoaminoglycans («chondronegative effect»). Discusses the place of topical forms of NSAIDs in the treatment of patients with osteoarthritis in accordance with the recommendations of the International society for the use of topical forms of NSAIDs in the management of patients with osteoarthritis of large and small joints. Data on transdermal transport of the topical form of diclofenac, a small molecule with lipophilic properties, are presented. Data on the effectiveness of topical forms of diclofenac in comparison with oral forms are presented according to numerous randomized controlled trials, and the comparable effectiveness of both forms of diclofenac is demonstrated, with maximum safety of the topical form. A special structure of Voltaren® Emulgel (Voltaren® Emulgel), combining the properties of a gel and cream, which provides rapid transdermal penetration and longer retention of the active substance in the area of inflammation, is described, as well as a special prolonged form of Voltaren® Emulgel), which creates additional convenience for use.