Juliana Hülsmann

The effective pharmacological treatment of inflamed wounds such as pyoderma gangraenosum remains challenging, as the systemic application of suitable drugs such as glucocorticoids is compromised by severe side effects and the inherent difficulties of wounds as drug targets. Furthermore, conventional semi-solid formulations are not suitable for direct application to open wounds. Thus, the treatment of inflamed wounds could considerably benefit from the development of active wound dressings for the topical administration of anti-inflammatory drugs. Although bacterial cellulose appears to be an ideal candidate for this purpose due to its known suitability for advanced wound care and as a drug delivery system, the incorporation of poorly water-soluble compounds into the hydrophilic material still poses a problem. The use of microemulsions could solve that open issue. The present study therefore explores their use as a novel approach to incorporate poorly water-soluble glucocorticoids into bacterial cellulose. Five microemulsion formulations were loaded with hydrocortisone or dexamethasone and characterized in detail, demonstrating their regular microstructure, biocompatibility and shelf-life stability. Bacterial cellulose was successfully loaded with the formulations as confirmed by transmission electron microscopy and surprisingly showed homogenous incorporation, even of w/o type microemulsions. High and controllable drug permeation through Strat-M^® membranes was observed, and the anti-inflammatory activity for permeated glucocorticoids was confirmed in vitro. This study presents a novel approach for the development of anti-inflammatory wound dressings using bacterial cellulose in combination with microemulsions.

RNA interference can be applied to different target genes for treating a variety of diseases, but an appropriate delivery system is necessary to ensure the transport of intact siRNAs to the site of action. In this study, cellulose was dually modified to create a non-viral vector for HDAC3 short interfering RNA (siRNA) transfer into cells. A guanidinium group introduced positive charges into the cellulose to allow complexation of negatively charged genetic material. Furthermore, a biotin group fixed by a polyethylene glycol (PEG) spacer was attached to the polymer to allow, if required, the binding of targeting ligands. The resulting polyplexes with HDAC3 siRNA had a size below 200 nm and a positive zeta potential of up to 15 mV. For N/P ratio 2 and higher, the polymer could efficiently complex siRNA. Nanoparticles, based on this dually modified derivative, revealed a low cytotoxicity. Only minor effects on the endothelial barrier integrity and a transfection efficiency in HEK293 cells higher than Lipofectamine 2000^TM were found. The uptake and release of the polyplexes were confirmed by immunofluorescence imaging. This study indicates that the modified biopolymer is an auspicious biocompatible non-viral vector with biotin as a promising moiety.