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Review

Journal of Pharmacy And Pharmacology

A review of bacterial cellulose-based drug delivery systems: their biochemistry, current approaches and future prospects Muhammad Mustafa Abeera, Mohd Cairul Iqbal Mohd Amina and Claire Martinb a Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia and bDepartment of Pharmacy, University of Wolverhampton, Wolverhampton, UK

Keywords bacterial cellulose; drug delivery; hydrogel; nanocellulose; nata de coco Correspondence Mohd Cairul Iqbal Mohd Amin, Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. E-mail: [email protected] Received October 11, 2013 Accepted January 18, 2014 doi: 10.1111/jphp.12234

Abstract Objectives The field of pharmaceutical technology is expanding rapidly because of the increasing number of drug delivery options. Successful drug delivery is influenced by multiple factors, one of which is the appropriate identification of materials for research and engineering of new drug delivery systems. Bacterial cellulose (BC) is one such biopolymer that fulfils the criteria for consideration as a drug delivery material. Key findings BC showed versatility in terms of its potential for in-situ modulation, chemical modification after synthesis and application in the biomedical field, thus expanding the current, more limited view of BC and facilitating the investigation of its potential for application in drug delivery. Summary Cellulose, which is widely available in nature, has numerous applications. One of the applications is that of BC in the pharmaceutical and biomedical fields, where it has been primarily applied for transdermal formulations to improve clinical outcomes. This review takes a multidisciplinary approach to consideration of the feasibility and potential benefits of BC in the development of other drug delivery systems for various routes of administration.

Introduction Cellulose, which is synthesised by members of the kingdoms Plantae and Animalia as well as the domain Eubacteria, is the most abundant product on earth. Within the animal kingdom, Urochordates (tunicates) such as Microcosmus fulcatus have the unique property of being able to produce rod-shaped crystals of cellulose, and therefore, contribute to cellulose synthesis.[1] The availability of extremely heterogeneous sources has led to many variations of cellulose, although the varieties share many features. Biochemically, cellulose is a polysaccharide with a β-1,4-glycosidic linkage, formed after condensation polymerisation of long chains of anhydroglucose units. In plants, 36 individual cellulose molecule chains pack together through hydrogen bonding to ultimately form ‘microfibrils’ in the order of 50 nm in diameter, which contain both amorphous and crystalline regions.[2] Cellulose microfibrils obtained from tunicates can be subjected to sulfuric acid hydrolysis and subsequently, led to the formation of nanocrystals. The elastic moduli of microfibrillar and nanocrystalline forms were found to be 145.2 ± 31.3

and 150.7 ± 28.8 GPa, which implied that the elastic moduli of the fibrillar and crystalline forms were in agreement with each other and they could be used interchangeably for imparting mechanical strength to composites.[3] Moreover, a view of the various morphological forms in addition to the microfibrils is required to account for the variety of cellulose forms in existence. In contrast to the fibres, cellulose may exist as ‘nanocrystalline’ cellulose (NCC). This negatively charged form is often obtained from acid hydrolysis and has specific physicochemical properties, including high-specific strength, surface properties and asymmetry.[4] Cellulose ‘nanowhiskers’ (CNWs) are another form of cellulose that can be obtained from a number of sources, including tunicates. The whiskers have a unique ability to act as reinforcing material for several polymers, and further confirm the need for differential elucidation of the data related to cellulose variation. It is also worth emphasising that the variation discussed here is not related to allomorphs of cellulose.[5] CNWs and NCC are terms that are sometimes used interchangeably (Figure 1).[6]

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

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Review of BC-based drug delivery systems

Muhammad Mustafa Abeer et al.

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Figure 1 (a & b) Represent microfibrils at different magnifications (scanning electron microscopy). (Reproduced from Kim et al. Surface acetylation of bactetial cellulose. Cellulose 2002; 9: 361–367). (c) represents nanocrystals (transmission electron microscopy) obtained from nata de coco (Reproduced from Johari et al. Comparison Study of hydrogels properties synthesised with micro-size and nano-size bacterial cellulose particles extracted from nata de coco. Chem Biochem Eng Q 2012; 26: 399–404.)

A consideration of the nanocrystallinity of cellulose leads directly to bacterial cellulose (BC), because this is synthesised in highly crystalline forms by the model organism, Gluconacetobacter xylinus (G. xylinus), which is the most widely studied source of BC.[7] It is necessary then to explain the fundamentals of BC in addition to those mentioned earlier for cellulose in general. It can help to understand the nature of BC and then move towards its applications in drug delivery. The synthesis and translocation of versatile BC is mediated by a complex of the translocation intermediate proteins BcsA and BcsB, as demonstrated in a model of Rhodobacter spheroids.[8] This model provides insight into the genetic characterisation of the biosynthetic machinery of BC, which can be used to investigate optimal conditions for translocation of the cellulose polymer. Plant cellulose is produced as lignocellulosic polymer, which is unlike purely synthesised BC. Moreover, its high surface area, degree of polymerisation, wet tensile strength, purity, crystallinity and nanostructured fibres differentiate it from plant cellulose.[9] Furthermore, BC is known to be biocompatible, perhaps because of its flexibility and porosity, resembling properties of collagen in the human body. The stability of cellulose at a wide range of temperatures also makes it amenable to heat sterilisation.[10] It can be purified using sodium hydroxide, yielding a form of BC with endotoxin values of

A review of bacterial cellulose-based drug delivery systems: their biochemistry, current approaches and future prospects.

The field of pharmaceutical technology is expanding rapidly because of the increasing number of drug delivery options. Successful drug delivery is inf...
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