Monitoring drug release from electrospun fibers using an in situ fiber-optics system

Electrospun fiber mats are currently gaining attention as advanced drug delivery systems. Dissolution testing for such systems is generally performed in small vials by immersing the fiber mats in buffered solutions. Defined aliquots of dissolution medium are withdrawn at predefined time points, and the dissolved drug is quantified. However, this procedure is associated with several drawbacks. The method is not automated, and as such requires manual sampling, which potentially leads to inaccuracies particularly in frequent sampling intervals as required for characterization of rapid drug release. Further, the sheet-like fiber mats tend to partially fold upon contact with the dissolution medium, which may potentially affect the release kinetics and reproducibility of the acquired release data. In this study, we investigated the application of a fully automated fiber-optics based dissolution testing system for in situ monitoring of drug release from electrospun fiber mats. Electrospun poly (vinyl alcohol) fibers loaded with lysozyme were used as a model system. To prevent folding of the fiber mats and ensure a fixed position in the dissolution vessel throughout the experiment, a flexible adapter was developed to allow for the attachment of the fiber mats to the vessel walls. Lysozyme release from the fiber mats was compared with the release from cast films with the same composition. Even though the release processes were rather fast and differences in release kinetics of the two systems were marginal, the fiber-optics based dissolution setup allowed for the successful detection of released protein in both cases. The present study, therefore, highlights the potential for the utilization of fully automated fiber-optics based dissolution testing systems for advanced in situ monitoring of drug release from electrospun fibers

Vibrational spectroscopic imaging and live cell video microscopy for studying differentiation of primary human alveolar epithelial cells.

Vukosavljevic B, Hittinger M, Hachmeister H, et al. Vibrational spectroscopic imaging and live cell video microscopy for studying differentiation of primary human alveolar epithelial cells. Journal of Biophotonics. 2019;12(6): e201800052

Skin penetration behavior of lipid-core nanocapsules for simultaneous delivery of resveratrol and curcumin

Polyphenols, which are secondary plant metabolites, gain increasing research interest due to their therapeutic potential. Among them, resveratrol and curcumin are two agents showing antioxidant, anti-inflammatory, antimicrobial as well as anticarcinogenic effects. In addition to their individual therapeutic effect, increased activity was reported upon co-delivery of the two compounds. However, due to the poor water solubility of resveratrol and curcumin, their clinical application is currently limited. In this context, lipid-core nanocapsules (LNC) composed of an oily core surrounded by a polymeric shell were introduced as drug carrier systems with the potential to overcome this obstacle. Furthermore, the encapsulation of polyphenols into LNC can increase their photostability. As the attributes of the polyphenols make them excellent candidates for skin treatment, the aim of this study was to investigate the effect of co-delivery of resveratrol and curcumin by LNC upon topical application on excised human skin. In contrast to the formulation with one polyphenol, resveratrol penetrated into deeper skin layers when the co-formulation was applied. Based on vibrational spectroscopy analysis, these effects are most likely due to interactions of curcumin and the stratum corneum, facilitating the skin absorption of the co-administered resveratrol. Furthermore, the interaction of LNC with primary human skin cells was analyzed encountering a cellular uptake within 24 h potentially leading to intracellular effects of the polyphenols. Thus, the simultaneous delivery of resveratrol and curcumin by LNC provides an intelligent way for immediate and sustained polyphenol delivery for skin disease treatment

Coherent anti-stokes Raman scattering microscopy to monitor drug dissolution in different oral pharmaceutical tablets

Coherent anti-Stokes Raman scattering (CARS) microscopy is used to visualize the release of a model drug (theophylline) from a lipid (tripalmitin) based tablet during dissolution. The effects of transformation and dissolution of the drug are imaged in real time. This study reveals that the manufacturing process causes significant differences in the release process: tablets prepared from powder show formation of theophylline monohydrate on the surface which prevents a controlled drug release, whereas solid lipid extrudates did not show formation of monohydrate. This visualization technique can aid future tablet design

Submicron polymeric particles prepared by vibrational spray-drying: Semisolid formulation and skin penetration/permeation studies.

Topical glucocorticoids (TG) such as dexamethasone (DEX) have been used for decades for the treatment of skin diseases. However, TG present well-documented side effects and their delivery to the skin is often insufficient. Therefore, many efforts have been undergone to improve the amount of drug delivered to the skin and to reduce side effects at the same time. In this work, the feasibility of DEX-submicron polymeric particles (SP) prepared by vibrational spray-drying as an approach to overcome the challenges associated with the topical administration of this drug class was evaluated. DEX was homogeneously dispersed in the SP matrix, according to confocal Raman microscopy analysis. Drug-loaded SP were incorporated into the oil phase of oil-in-water emulsions (creams). The formulation containing polymeric submicron particles (C-SP) showed controlled drug release kinetics and a significant drug accumulation in skin compared to formulations containing non-polymeric particles or free drug. DEX accumulation in the stratum corneum was evaluated by tape stripping and a depot effect over time was observed for C-SP, while the formulation containing the free drug showed a decrease over time. Similarly, C-SP presented higher drug retention in epidermis and dermis in skin penetration studies performed on pig skin in Franz diffusion cells, while drug permeation into the receptor compartment was negligible. It was demonstrated, for the first time, the advantageous application of submicron polymeric particles obtained by vibrational spray-drying in semisolid formulations for cutaneous administration to overcome challenges related to the therapy with TG such as DEX