Hyaluronic acid (HA) hydrogels are interesting delivery systems for topical applications. Besides moisturizing the skin and improving wound healing, HA facilitates topical drug absorption and is highly compatible with labile biomacromolecules. Hence, in this study we investigated the influence of HA hydrogels with different molecular weights (5 kDa, 100 kDa, 1 MDa) on the skin absorption of the model protein bovine serum albumin (BSA) using fluorescence lifetime imaging microscopy (FLIM). To elucidate the interactions of HA with the stratum corneum and the skin absorption of HA itself, we combined FLIM and Fourier-transform infrared (FTIR) spectroscopy. Our results revealed distinct formulation and skin-dependent effects. In barrier deficient (tape-stripped) skin, BSA alone penetrated into dermal layers. When BSA and HA were applied together, however, penetration was restricted to the epidermis. In normal skin, penetration enhancement of BSA into the epidermis was observed when applying low molecular weight HA (5 kDa). Fluorescence resonance energy transfer analysis indicated close interactions between HA and BSA under these conditions. FTIR spectroscopic analysis of HA interactions with stratum corneum constituents showed an α-helix to β-sheet interconversion of keratin in the stratum corneum, increased skin hydration, and intense interactions between 100 kDa HA and the skin lipids resulting in a more disordered arrangement of the latter. In conclusion, HA hydrogels restricted the delivery of biomacromolecules to the stratum corneum and viable epidermis in barrier deficient skin, and therefore seem to be potential topical drug vehicles. In contrast, HA acted as an enhancer for delivery in normal skin, probably mediated by a combination of cotransport, increased skin hydration, and modifications of the stratum corneum properties.
Structural changes within dendritic polymer scaffolds may influence the polymer's behavior in biological relevant systems such as tissues and cells. A dendritic polyglycerol sulfate (dPGS) was recently found to act as an inhibitor of inflammatory processes. Here, we investigated the molecular dynamics and environmental sensitivity of dPGS using an indocarbocyanine (ICC) labeled variant (dPGS-ICC). The environmental sensitivity was demonstrated by UV/Vis and fluorescence spectroscopic characterization of dPGS-ICC in different solvents. In particular, fluorescence lifetime measurements revealed additional information on the local dye environment that manifest themselves in characteristic fluorescence lifetime signatures depending on the solvent. Furthermore, the interaction of dPGS-ICC with a model cell system-giant unilamellar vesicles (GUVs)-was studied with fluorescence lifetime imaging microscopy. We observed that dPGS-ICC is enriched in the membrane but does not penetrate into the lumen of the GUV. The characteristic lifetime signature of dPGS-ICC within the lipid membrane (τ mean = 1.6 ns) was clearly different from that obtained for dPGS-ICC in aqueous solution (τ mean = 0.42 ns) and can thus be employed to dissect differential interactions of dPGS in tissue. By using time-resolved fluorescence depolarization, we further showed that the size of dPGS shrinks by nearly 50% above 30°C. These results contribute to a further understanding of dPGS structure and dynamics and may help to provide tailor-made polymer architectures for biomedical applications.
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