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Imiquimod (IMQ) is an immunostimulating agent used in the treatment of basal cell carcinoma and actinic keratosis. Due to its low solubility and poor skin bioavailability, the dermal formulation of IMQ remains challenging. In analogy to tyre compounds used in Formula 1 racing, we compare four types of nanosystems belonging to three groups: (i) "hard" nanoparticles in the form of IMQ nanocrystals, (ii) "intermediate" nanoparticles in the form of liposomes and lipid nanocapsules, and (iii) "soft" nanoparticles in the form of a nanoemulsion based on oleic acid. The nanoemulsion and nanocrystals were able to incorporate the highest amount of IMQ (at least 2 wt%) compared to liposomes (0.03 wt%) and lipid nanocapsules (0.08 wt%). Regarding size, liposomes, and lipid nanocapsules were rather small (around 40 nm) whereas nanocrystals and nanoemulsion were larger (around 200 nm). All developed nanoformulations showed high efficiency to deliver IMQ into the skin tissue without undesirable subsequent permeation through the skin to acceptor. Especially, the 2 wt% IMQ nanoemulsion accumulated 129 μg/g IMQ in the skin, compared to 34 μg/g of a 5 wt% commercial cream. The effects of the respective nanoparticulate systems were discussed with respect to their possible diffusion kinetics (Brownian motion vs. settling) in the aqueous phase., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The sorption of poorly aqueous soluble active pharmaceutical ingredients (API) to mesoporous silica carriers is an increasingly common formulation strategy for dissolution rate enhancement for this challenging group of substances. However, the success of this approach for a particular API depends on an array of factors including the properties of the porous carrier, the loading method, or the attempted mass fraction of the API. At present, there is no established methodology for the rational selection of these parameters. In the present work, we report a systematic comparison of four well-characterised silica carriers and seven APIs loaded by the same solvent evaporation method. In each case, we find the maximum amorphization capacity by x-ray powder diffraction analysis and measure the in vitro drug release kinetics. For a selected case, we also demonstrate the potential for bioavailability enhancement by a permeation essay., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Diseases related to a disrupted skin barrier are accompanied by lower levels of ceramides in the stratum corneum (SC) lipid matrix. Delivering ceramides directly into damaged skin is a viable alternative to conventional corticosteroids, but is hindered by their low skin bioavailability and limited nanoformulation ability. Here, we developed stable liposomal systems containing ceramides and other SC lipids, and tested their effectiveness in skin barrier repair. Lipid film hydration and high-pressure homogenization were used to prepare different types of liposomes. To determine the stability, the particle size and polydispersity index were measured. The optimal systems were found to include ceramide 3 and 6, cholesterol and stearic acid, with 10% urea in phosphate-buffered saline as the aqueous phase. The ability of the system to repair chemically-damaged porcine skin was tested. While treatment by a standard lipid suspension reduced the passage of a model permeant only to a limited extent, drug flux through the liposomally-treated skin was much closer to permeation through intact skin. The non-homogenized liposomes were more effective than their homogenized version. These findings were also confirmed by FTIR measurements. This suggests that our approach to liposomal development has considerable potential for the repair of a disrupted skin barrier., (Copyright © 2021 Elsevier B.V. All rights reserved.)