Nanocellulose-Based Film-Forming Hydrogels for Improved Outcomes in Atopic Skin.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by impaired skin barrier function. Amongst the various dermal formulations that are being used and/or investigated for AD treatment, one of the advanced approaches is the use of hydrogels as film-forming systems that are applied directly to the skin and have the added value of providing a physical barrier, which is lacking in atopic skin. Novel film-forming hydrogels based on two different nanocrystalline celluloses (NCCs) in combination with one of two natural polymers (alginate or pectin) were developed for incorporation of betamethasone dipropionate (BDP). Initially, the low water solubility of BDP was resolved by prior dissolution in a self-microemulsifying drug delivery system (SMEDDS). The mixture of Kolliphor® EL/Capryol® 90 in a ratio of 8/2 was chosen on the merit of its high BDP-saturated solubility and no BDP precipitation upon water dilution, enabling BDP to remain dissolved after incorporation into hydrogels. The solvent evaporation method was used to prepare the films, and their high water retention capacity was confirmed in vitro on artificial membranes and pig ear skin. The presented results thus confirm NCC-based film-forming hydrogels as a very promising drug delivery system for AD treatment.

Relative bioavailability enhancement of simvastatin via dry emulsion systems: Comparison of spray drying and fluid bed layering technology.

Comprehensive comparisons of similar lipid based drug delivery systems produced by different technologies are scarce. Spray drying and fluid bed layering technologies were compared with respect to the process and product characteristics of otherwise similar simvastatin loaded dry emulsion systems. Fluid bed layering provided higher process yield (83.3% vs 71.5%), encapsulation efficiency (80.0% vs 68.4%), relative one month product stability (93.8% vs 85.5%), larger and more circular particles (336 µm vs 56 µm) and lower median oil droplet size after product reconstitution in water (2.85 µm vs 4.27 µm), compared to spray drying. However, spray dried products exhibited higher drug content (22.2 mg/g vs 9.34 mg/g). An in-vivo pharmacokinetic study in rats was performed and a pharmacokinetic model was developed in order to compare the optimised simvastatin loaded dry emulsion systems, a simvastatin glyceride mimetic loaded in the dry emulsion and a simvastatin loaded SMEDDS with a reference physical mixture. Of the formulation tested, fluid bed layered pellets excelled and provided a 115% relative increase in bioavailability. Among the two technologies, fluid bed layering provided dry emulsion products with higher relative bioavailability and better product characteristics for further processing into final dosage forms.

Lamellar liquid crystals maintain keratinocytes' membrane fluidity: An AFM qualitative and quantitative study.

Despite extensive investigations of lamellar liquid crystals for dermal application, the effects of these systems at the cellular level are still not well elucidated. The key aim of this study was to determine the elasticity and morphological features of keratinocytes after exposure to a lamellar liquid crystal system (LLCS) using atomic force microscopy (AFM) as the method of choice. Prior to AFM assessment, a cell proliferation test and light plus fluorescence imaging were applied to determine the sub-toxic concentration of LLCS. According to the AFM results, slightly altered morphology was observed in the case of fixed keratinocytes, while an intact morphology was visualized on live cells. From the quantitative study, decreased Young's moduli were determined for fixed cells (i.e., 8.6 vs. 15.2 MPa and 1.3 vs. 2.9 MPa for ethanol or PFA-fixed LLCS-treated vs. control cells, respectively) and live cells (i.e., ranging from 0.6 to 2.8 for LLCS-treated vs. 1.1-4.5 MPa for untreated cells), clearly demonstrating increased cell elasticity. This is related to improved membrane fluidity as a consequence of interactions between the acyl chains of cell membrane phosphatidylcholine and those of LLCS. What seems to be of major importance is that the study confirms the potential clinical relevance of such systems in treatment of aged skin with characteristically more rigid epithelial cells.