Plamen Kirilov

Modulation of transepithelial electric resistance (TEER) in reconstructed human epidermis by excipients known to permeate intestinal tight junctions.

Several excipients are commonly used to enhance the drug absorption through simple epithelia of the digestive tract. They permeate the paracellular barrier constituted by tight junctions (TJs). We compared the effects of two excipients, sodium caprate (C10) and a self‐emulsifying excipient Labrasol composed of a mixture of caprylocaproyl polyoxyl‐8 glycerides, both applied to emerged reconstructed human epidermis either ‘systemically’, that is by addition to the culture medium, or topically. During the ‘systemic’ application, which produced cytoplasmic translocation of occludin and leakage of the biotin marker into the lower stratum corneum, the decrease in the trans‐epithelial electrical resistance (TEER) was less abrupt with Labrasol when compared with C10, even though both excipients produced comparable final effects over time. With topical Labrasol, a significant TEER decrease was obtained with 5 times the ‘systemic’ concentrations. Topical application of C10 also resulted in the loss of the barrier function measured with TEER but had dramatic deleterious effects on the tissue morphology observed with light and electron microscopy. Our study demonstrates the potential value of Labrasol as an enhancer of bioavailability of molecules applied through the transcutaneous route. Our results suggest modulation of the epidermal TJs by both compounds. Even though the C10 action was at least partly due to overall cell damage and despite the fact that the decrease in TEER after topical application was apparently related to the permeabilization of the primary barrier of the stratum corneum in the first place.

Organogels, promising drug delivery systems: an update of state-of-the-art and recent applications

ABSTRACT Organogels are semi‐solid systems with an organic liquid phase immobilized by a three‐dimensional network composed of self‐assembled, crosslinked or entangled gelator fibers. Organogel applications are various, including chemistry, pharmaceuticals, cosmetics, biotechnologies and food technology. In pharmacology, they are used as drug and vaccine delivery platforms for active ingredients via diverse routes such as transdermal, oral and parenteral. In a close past, their uses as drug delivery systems have been unfortunately hampered by the toxicity of the selected organic solvents. More recently, the synthesis of more biocompatible organogels has strengthened the development of several biomedical and pharmaceutical applications. This review provides a global view of organogels, such as nature, syntheses, characterizations and properties. An emphasis is placed on the most recent technologies used in the design of organogels as potential controlled delivery systems. A particular attention is provided to their newest therapeutic applications. Graphical abstract Owing their gel‐sol transition, organogels issued from organogelators organized in biocompatible organic solvents present various drug release profiles. Adapted to broad applications, they are versatile controlled released systems. Figure. No caption available.

Thermosensitive Hydrogels in Dermatology: A Multidisciplinary Overview

Formulation of dermatological medicines in hospitals is a multidisciplinary challenge addressing pharmaceutical issues such as (1) excipient availability and safety, (2) drug solubility and diffusivity, (3) drug-excipient compatibility, (4) formulation stability, and (5) convenience of use. Thermosensitive hydrogels are polymeric excipients that exhibit interesting properties, especially solubilizing properties and the ability to physically respond to thermal physiological stimuli. The inclusion of such polymers in dermatological formula enables to produce “intelligent medicines” that outgrow problems encountered with conventional formulations and to design novel delivery systems. This chapter will detail pharmaceutical considerations about excipient choice and thermosensitive polymers and illustrate the possibilities they offer by various formulation and clinical application examples.