# Bacterial Cellulose-Polyvinyl Alcohol Based Complex Composites for Controlled Drug Release
###### Abstract  
Drug-loaded mono- and multilayer composite membranes were prepared. The composites, based on nano-fibrilated bacterial cellulose, nano-powdered bacterial cellulose, and polyvinyl alcohol, all biocompatible and biodegradable, were characterized in terms of basic factors related to drug diffusivity and mass transfer: swelling ability, water solubility, and water vapor permeability. Tetracycline hydrochloride was used in this case as drug model. Drug release was evaluated in an aqueous environment for two concentration levels of the antibiotic, and mathematical modeling was applied to fit experimental data. Tetracycline release was influenced by a membranes' structure, layers' composition, and by a membranes' thickness. Bacterial cellulose nanofibrils proved to be the key factor in achieving suitable drug release profiles. Thus, sustained antibiotic delivery was obtained for several days in the case of multilayer composites. The composites proved drug stability and antibacterial efficiency before and after TC-HCl continuous release for several days.  
polyvinyl alcohol; bacterial cellulose; multilayer composites; diffusion; controlled release; mathematical modeling +
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BC, as versatile biopolymer, with exceptional conformation and properties, is extensively studied and used in a wide variety of applications/industries, as many review articles are indicating, including very recent ones [11; 12; 13; 14; 15; 16; 17; 18]. BC favors cell adhesion and proliferation; its deformability resembles soft tissue and is non-allergenic. Furthermore, its degradation product is glucose; thus, the usage of BC as biomaterial no longer needs to be questioned [19]. Biocompatibility, non-toxicity, and high liquid retention capacity are the main features that recommend it for drug delivery and wound healing [14]. In this work, two forms of BC were used to investigate the effect on drug release, since it has been proved that by disrupting the natural 3D structure of BC (to obtain nanofibrils or nanoparticles) the properties of the resulting composite materials containing them, can be changed (swelling, crystallinity) [20; 21].  
PVA-based materials are extensively applied in the medical field. Among many attributes (thermal and chemical stability, film forming ability), PVA is well known as non-toxic and biocompatible with living cells/tissues [22]. Moreover, it was shown in previous research that BC improves cells viability in cytotoxicity evaluations of pure PVA [23].  
The goal of our research was to develop novel and versatile structures, based on well-known biodegradable and biocompatible materials, to hinder initial burst release and, at the same time, to provide retarded and/or adjustable drug release. Although there are many known preparation methods for wound dressing films, we chose to prepare the composites using the conventional solvent casting method, due to facile and low-cost processing, and suitability for polymeric dispersions [24].  
To the authors' knowledge, this is the first study to develop complex composites, based on two forms of BC, to the benefit of different physico-chemical characteristics depending on the BC type, and PVA. Given recent studies reported in the literature, and based on the authors' knowledge and expertise, the resulting composites should exhibit non-toxicity and excellent biocompatibility [23; 25].  
The main objectives were to evaluate the materials' structural characteristics, water and water vapor transport properties, antibacterial activity and, more importantly, to prove the purposed applicability: controlled drug release. To evaluate TC-HCl diffusivity, the process was assessed experimentally and by mathematical modeling. Mathematical models were applied to fit the experimental data, to evaluate drug release processes, and to identify the influencing factors on the overall mass transfer rate. The obtained materials provided mass transfer limitations necessary to achieve beneficial drug release.