Nadine Hessler

The Biopolymer Bacterial Nanocellulose as Drug Delivery System: Investigation of Drug Loading and Release using the Model Protein Albumin

Although bacterial nanocellulose (BNC) has reached enormous interest for biomedical applications because of its outstanding material properties, investigations about its potential as drug delivery system are very rare. In the present study, for the first time, the applicability of BNC as drug delivery system for proteins using serum albumin as model drug was systematically investigated. Additionally, never-dried BNC was compared with freeze-dried BNC. For both types of BNC, a dependency of concentration, temperature, time, and preswelling for albumin loading and release could be demonstrated. These findings indicated an overlay of diffusion- and swelling-controlled processes, which could be confirmed by Ritger-Peppas equation. Freeze-dried samples showed a lower uptake capacity for albumin than native BNC, which was found to be related to changes of the fiber network during the freeze drying process as demonstrated by electron microscopy and protein staining experiments. The integrity and biological activity of proteins could be retained during the loading and release processes, which was demonstrated by gel electrophoresis and the use of luciferase as biologically active molecule. In conclusion, hydrophilicity, high biocompatibility, and controllable drug loading and release render BNC an innovative and attractive biopolymer for controlled drug delivery.

Active wound dressings based on bacterial nanocellulose as drug delivery system for octenidine

Although bacterial nanocellulose (BNC) may serve as an ideal wound dressing, it exhibits no antibacterial properties by itself. Therefore, in the present study BNC was functionalized with the antiseptic drug octenidine. Drug loading and release, mechanical characteristics, biocompatibility, and antimicrobial efficacy were investigated. Octenidine release was based on diffusion and swelling according to the Ritger-Peppas equation and characterized by a time dependent biphasic release profile, with a rapid release in the first 8h, followed by a slower release rate up to 96 h. The comparison between lab-scale and up-scale BNC identified thickness, water content, and the surface area to volume ratio as parameters which have an impact on the control of the release characteristics. Compression and tensile strength remained unchanged upon incorporation of octenidine in BNC. In biological assays, drug-loaded BNC demonstrated high biocompatibility in human keratinocytes and antimicrobial activity against Staphylococcus aureus. In a long-term storage test, the octenidine loaded in BNC was found to be stable, releasable, and biologically active over a period of 6 months without changes. In conclusion, octenidine loaded BNC presents a ready-to-use wound dressing for the treatment of infected wounds that can be stored over 6 months without losing its antibacterial activity.

White biotechnology for cellulose manufacturing—The HoLiR concept

A variety of approaches are available for generation of bacteria‐produced nanocellulose (BNC) in different forms. BNC production under static cultivation conditions usually results in fleeces or foils, characterized by a homogeneous, three‐dimensional network of nanofibers and a uniform surface. However, under static cultivation conditions in batch vessels, the widths and the lengths of the BNC sheets cultured are determined by the dimensions of the culture vessel. In this contribution, a novel, efficient process for a (semi‐)continuous cultivation of planar BNC fleeces and foils with a freely selectable length and an adjustable height is presented. By means of comprehensive investigations, the comparability of the BNC harvested to that gained from static cultivation under batch conditions is demonstrated. A first estimation of the production costs further shows that this type of processing allows for significant cost reductions compared to static cultivation of BNC in Erlenmeyer flasks. Biotechnol. Bioeng. 2010. 105: 740–747.

Antimicrobial functionalization of bacterial nanocellulose by loading with polihexanide and povidone-iodine

Bacterial nanocellulose (BNC) is chemically identical with plant cellulose but free of byproducts like lignin, pectin, and hemicelluloses, featuring a unique reticulate network of fine fibers. BNC sheets are mostly obtained by static cultivation. Now, a Horizontal Lift Reactor may provide a cost efficient method for mass production. This is of particular interest as BNC features several properties of an ideal wound dressing although it exhibits no bactericidal activity. Therefore, BNC was functionalized with the antiseptics povidone-iodine (PI) and polihexanide (PHMB). Drug loading and release, mechanical characteristics, biocompatibility, and antimicrobial efficacy were investigated. Antiseptics release was based on diffusion and swelling according to Ritger–Peppas equation. PI-loaded BNC demonstrated a delayed release compared to PHMB due to a high molar drug mass and structural changes induced by PI insertion into BNC that also increased the compressive strength of BNC samples. Biological assays demonstrated high biocompatibility of PI-loaded BNC in human keratinocytes but a distinctly lower antimicrobial activity against Staphylococcus aureus compared to PHMB-loaded BNC. Overall, BNC loaded with PHMB demonstrated a better therapeutic window. Moreover, compressive and tensile strength were not changed by incorporation of PHMB into BNC, and solidity during loading and release could be confirmed.

Bacterial nanocellulose with a shape-memory effect as potential drug delivery system

In the steadily emerging field of applications for the natural biopolymer bacterial nanocellulose (BNC), the development of environmentally-friendly and cost-saving techniques to form xerogels by partial or complete dewatering is of great interest for convenient storage, handling and a reduced risk of microbial contamination. Air-dried BNC itself is not able to rehydrate after complete drying due to a structural collapse. In the present paper, it was supplemented with different hydrophilic, water-binding additives and characterized regarding morphology, re-swelling behavior, mechanical stability and potential as drug delivery system. A fast rehydration could be obtained by the addition of magnesium chloride > glucose > sucrose > sorbitol, with a maximum re-swelling percentage up to about 88% (magnesium chloride) of the initial wet weight. In contrast, poly(ethylene glycol) (8 kDa), lactose and trehalose reached only 12–30% whereas mannitol and sodium chloride only had a negligible effect. A high re-swelling value was found to be correlated with the preservation of the three-dimensional BNC network structure and mechanical characteristics such as compression and tensile strength. Confirming the relevance of these findings, the use of the hydrophilic model drug azorubine demonstrated the applicability of the shape-memorized bacterial nanocellulose as drug delivery system with controllable release profiles.

Loading of bacterial nanocellulose hydrogels with proteins using a high-speed technique

For the loading of the natural biopolymer bacterial nanocellulose (BNC) with drugs, usually an adsorption method has been described. In the present study, a high-speed loading technique based on vortexing was established for the incorporation of proteins in BNC as drug delivery system. Compared to the conventional technique, vortexing accomplished in 10 min the same protein loading capacity as the adsorption method in 24h with comparable protein distribution and protein stability. Vortex loaded BNC demonstrated a retarded protein release with a lower total amount of released protein after 168 h compared to the adsorption loaded BNC. This was correlated with a densification of the fiber network as shown by electron microscopy and a reduced water holding capacity. These observations offer the possibility to control the drug release by selection of the preparation technique.