Pavel Berka

Ceramides in the skin lipid membranes: length matters.

Ceramides are essential constituents of the skin barrier that allow humans to live on dry land. Reduced levels of ceramides have been associated with skin diseases, e.g., atopic dermatitis. However, the structural requirements and mechanisms of action of ceramides are not fully understood. Here, we report the effects of ceramide acyl chain length on the permeabilities and biophysics of lipid membranes composed of ceramides (or free sphingosine), fatty acids, cholesterol, and cholesterol sulfate. Short-chain ceramides increased the permeability of the lipid membranes compared to a long-chain ceramide with maxima at 4-6 carbons in the acyl. By a combination of differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, Langmuir monolayers, and atomic force microscopy, we found that the reason for this effect in short ceramides was a lower proportion of tight orthorhombic packing and phase separation of continuous short ceramide-enriched domains with shorter lamellar periodicity compared to native long ceramides. Thus, long acyl chains in ceramides are essential for the formation of tightly packed impermeable lipid lamellae. Moreover, the model skin lipid membranes are a valuable tool to study the relationships between the lipid structure and composition, lipid organization, and the membrane permeability.

Electrospun drug loaded membranes for sublingual administration of sumatriptan and naproxen.

Sublingual administration of active pharmaceutical substances is in principle favourable for rapid onset of drug action, ready accessibility and avoidance of first pass metabolism. This administration could prove very useful in the treatment of migraines, thus two frequently used drugs were selected for our study. Sumatriptan succinate, naproxen, and its salt as well as combinations of these were incorporated into nanofibrous membranes via the electrospinning process. DSC measurements proved that the resulted membranes contained non-crystalline drug forms. SEM imaging approved good homogeneity of diameter and shape of the membrane nanofibres. The nanofibrous membranes always showed the rapid and mutually independent release of the tested drugs. The drugs exhibited very high differences in sublingual permeation rates in vitro, but the rates of both substances were increased several times using nanofibrous membranes as the drug carrier in comparison to drug solutions. The released drugs subsequently permeated through sublingual mucosa preferentially as non-ionized moieties. The prepared nanofibrous membranes proved very flexible and mechanically resistant. With their drug load capacity of up to 40% of membrane mass, they could be very advantageous for the formulation of sublingual drug delivery systems.

Influence of aggregation on interaction of lipophilic, water-insoluble azaphthalocyanines with DOPC vesicles.

Dioleoylphosphatidylcholine unilamellar vesicles made by extrusion technique (LUVETs) were studied as the delivery system for lipophilic water‐insoluble potential photosensitizers for photodynamic therapy (PDT). Two azaphthalocyanines (AzaPcs) with hydrophobic substituents only and two also possessing two charged amino groups were introduced into the study. All compounds are insoluble in water and form aggregates in PBS with tetrahydrofuran as cosolvent. The size of these aggregates depends on the concentration of AzaPc in solution. AzaPcs with tert‐butyl substituents were found to be incorporated into the lipid bilayer of vesicles in the monomeric form even at high concentrations. The stability of LUVETs with incorporated AzaPc was excellent for at least 4 weeks. Therefore, they are suitable for use as a delivery system for these water‐insoluble photosensitizers. Very low amount of AzaPc with n‐octyl substituents incorporated into LUVETs due to its stronger self‐aggregation. Values of binding constants determined for all AzaPcs showed inverse order than expected from their lipophilicities. However, the binding constants followed the order of the strength of aggregation forces. Aggregation of AzaPcs in water medium plays a very important role in the interaction of AzaPcs with LUVETs.