Do bacterial cellulose membranes have potential in drug-delivery systems?

1. Introduction

2. BC production

3. BC general applications

4. BC on modified drug-delivery

systems

5. Conclusion

6. Expert opinion

Review

Do bacterial cellulose membraneshave potential in drug-deliverysystems?Armando JD Silvestre†, Carmen SR Freire & Carlos P Neto†University of Aveiro, CICECO and Department of Chemistry, Aveiro, Portugal

Introduction: Bacterial cellulose (BC) is an extremely pure form of cellulose,

which, due to its unique properties, such as high purity, water-holding capac-

ity, three-dimensional nanofibrilar network, mechanical strength, biodegrad-

ability and biocompatibility, shows a high potential as nanomaterial in a wide

range of high-tech domains including biomedical applications, and most

notably in controlled drug-delivery systems.

Areas covered: This appraisal is intended to cover the major characteristics of

BC, followed by the key aspects of BC production both in static and agitated

conditions, and a glance of the major applications of BC, giving some empha-

sis to biomedical applications. Finally, a detailed discussion of the different

applications of BC in controlled drug-delivery systems will be put forward,

with focus on topical and oral drug-delivery systems, using either native BC

or composite materials thereof.

Expert opinion: The limited number of studies carried out so far demon-

strated that BC, or materials prepared from it, are interesting materials for

drug-delivery systems. There is, however, a large field of systematic research

ahead to develop new and more selectively responsive materials and eventu-

ally to conjugate them with other biomedical applications of BC under

development.

Keywords: bacterial cellulose, controlled drug delivery, dermal delivery system applications,

nanocomposites, oral delivery system applications

Expert Opin. Drug Deliv. [Early Online]

1. Introduction

Cellulose is the most abundant biological macromolecule on earth; it is mostlyobtained from plants, where it represents the main structural element of cell walls,and has a high economic importance in the pulp and paper industry as well as in thetextile sector [1-3]. However, cellulose is also produced by a family of sea animalscalled tunicates, some algae species and various aerobic non-pathogenic bacteria [1].Despite the origin, cellulose is a linear homopolymer of b-(1!4)-linkedD-glucopyranose units varying mainly on purity, degree of polymerization (DP)and crystallinity index [4].

Bacterial cellulose (BC) was first reported by Adrien Brown in 1886, whonoticed the formation of a very strong white gelatinous pellicle on the surface ofa liquid medium, while studying acetic fermentations, which could grow up to25 mm thick. This membrane was generated by a bacterium, named Bacterium xyli-num, later renamed Acetobacter xylinum and presently known as Gluconacetobacterxylinus [5,6].

It has been suggested that BC production is a mechanism used by bacteria tomaintain their position close to the culture medium surface, where there is a higheroxygen content, and it also serves as a protective coating against ultraviolet

10.1517/17425247.2014.920819 © 2014 Informa UK, Ltd. ISSN 1742-5247, e-ISSN 1744-7593 1All rights reserved: reproduction in whole or in part not permitted

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http://informahealthcare.com/journal/EDD

radiation, prevents the entrance of enemies and heavy-metalions, whereas nutrients diffuse easily throughout thepellicle [1,7].Other bacteria species from the genera Gluconacetobacer,

Sarcina and Agrobacterium, among others, have also beenreported to produce BC [4]. Gluconacetobacter xylinus is anon-pathogenic, rod-shaped, obligate aerobic Gram-negativebacterium, which can produce relatively high amounts ofBC from several carbon and nitrogen sources [4,8] and remainsas the reference strain for research and commercial BC pro-duction [9]. G. xylinus are ubiquitous in nature, being natu-rally present wherever the fermentation of sugars takes place,as, for example, on damaged fruits and unpasteurized juices,beers, wines, etc. [8]. Recently, a G. sacchari strain has alsobeen reported to produce BC with yields comparable to thoseobtained with G. xylinum using different carbonsources [10,11].BC production starts with the production of individual

b-(1!4) chains between the outer and plasma membranesof the cell. A single G. xylinus cell may polymerize up to200,000 glucose molecules per second into b-(1!4)glucanchains, followed by their release outwards through pores inthe cell surface [12]. BC chains then assemble into protofibrils,with ~2 -- 4 nm of diameter, which further gather into nano-fibrils of ~3 -- 15 nm thick and 70 -- 80 nm wide [1,4,13,14].Nanofibrils, in turn, entangle into a ribbon of semi-crystallinecellulose whose interwoven produces the BC fibrous network(Figure 1) [5,15-17].

2. BC production

BC can be produced in two distinct conditions, namely staticand agitated conditions, which affect significantly the mor-phology and physical and mechanical properties of the final

material and therefore might be chosen depending on theintended applications [18].

Static production is the most common process, yielding ahighly hydrated BC membrane (or pellicle) on the air--culturemedia interface (Figure 2) [7,19]. As BC is biosynthesized, amembrane with increasing thickness is produced and, sinceoxygen is required for bacteria to grow and for cellulose pro-duction, the mature BC membrane is constantly pusheddown as new cellulose is produced on the culture media--airinterface [13,16].

Under static conditions it is possible to obtain uniform andsmooth BC products with defined shapes, which can beemployed, for instance, in the biomedical field [20] as artificialblood vessels [16] or artificial skin [21]. Moldability of BC dur-ing biosynthesis and shape retention is a feature that mayenable the development of designed shape products directlyin the culture media [8,22], increasing its application range.

Under agitated conditions BC is produced in the form ofsmall pellets, fibers, irregular masses or spherical particlesinstead of membranes [23-25]. BC produced under agitatedconditions is similar in terms of chemical composition tothat obtained under static conditions but its nanofibers arecurved and entangled with one another, in contrast with thehighly extended ones attained under static conditions, result-ing in a denser structure. In addition, agitated BC has a lowerDP and crystallinity index, and higher water-holding capacitythan the one obtained under static conditions [19].

3. BC general applications

BC shows unique properties, which allow applications towhich plant cellulose is not suitable. First of all, it is producedin a highly pure form, completely free of hemicelluloses, lig-nin and pectins [4], making its purification a simpler processas compared to plant cellulose [9].

Native BC is a highly porous material with high permeabil-ity to liquids and gases and high water-uptake capacity (watercontent > 90%) [16], and these properties are due to BC ultra-fine network structure composed of ribbon-shaped nano- andmicrofibrils (Figure 1) [4], which is some 100 times thinnerthan those of plant cellulose fibers.

BC nanofibers show low density [26], and a high degree ofpolymerization (~ 2000 -- 6000) [4,27]. In addition, their largeaspect ratio and high surface area lead to strong interactionswith surrounding components, resulting, for example, in theretention of high amounts of water, strong interactions withother polymers and biomaterials, and fixation of differenttypes of nanoparticles [20,28-32]. Furthermore, the nanometricscale of BC fiber diameter imparts them with a feature that isnot achievable by vegetable fibers, that is, transparency, whichcan be quite attractive, if not determining for many applica-tions. BC shows also a high crystallinity index (60 -- 80%)[1,4,33,34], high mechanical strength, with a tensile strength of200 -- 300 MPa [1,4], and a Young’s modulus of up to15 GPa [1,4,16,35], as well as high thermal stability (with a

Article highlights.

. Bacterial cellulose (BC) can be efficiently produced understatic and agitated conditions using benign bacteriafrom the genera Gluconacetobacter.

. BC shows a panoply of promising applications innanocomposite materials.

. BC is a material with high potential for transdermaldelivery systems, even when compared to conventionaldelivery systems.

. BC and derived nanocomposites show promising pH-responsive properties for applications in oral drug-delivery systems.

. The combination of BC with other polymeric matricesresponsive to external/body stimuli and othermodification approaches opens new perspectives for thedesign of tailored drug-delivery systems based on thisnatural biopolymer.

This box summarizes key points contained in the article.

A. J. D. Silvestre et al.

2 Expert Opin. Drug Deliv. (2014) 11(7)

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decomposition temperature ranging between 340 and370�C) [36], which is a quite important parameter regardingthe sterilization procedures required for several biomedicaldevices and products.

The resistance to in vivo degradation, due to the absence ofcellulases in the human body, and low solubility of BC maybe advantageous for some tissue-engineering applications [37].Finally, the biocompatibility and non-toxicity of BC have alsobeen assessed, through in vitro and in vivo studies. Severalreports indicated that BC is not cytotoxic to Chinese hamsterovary, fibroblasts and endothelial cells, in vitro. Moreover, thein vivo toxicity of BC was investigated through its subcutane-ous implantation into rats and the implants evaluation withrespect to any sign of inflammation, foreign body responsesand cell viability [38]. The results attained revealed no macro-scopic signs of inflammation around the implants and allowedconcluding that BC was beneficial to cell attachment and

proliferation [38]. Another approach to these tests is throughthe intraperitoneal injection of various doses of BC nanofibersinto mice. After several days of exposure, blood samples werecollected and the results showed no effect on the biochemicalprofile between the control and mice exposed to BC [37]. Fur-thermore, in a recent skin compatibility study it was demon-strated that BC membranes produce no skin adverse reactions,and that when loaded with a small percentage of glycerol pro-duce a beneficial moisturizing effect [39].

One of the first uses of BC was in the production of atraditional Philippines dessert called ‘nata de coco’, whereBC is produced from coconut water fermentation and thencut into small pieces and immersed in a sugar syrup [1,7,28].BC has also been investigated as potential thickening, stabiliz-ing, gelling and suspending agent in the food industry [9].

Other applications include the BC utilization as a supportfor enzymes and cells immobilization [40-42], the production

Single microfiber Ribbon

Glucan chainaggregate

HO

HO

HO

OH

OH

OHOH

nOO O O

Figure 1. Scanning electron microscopy (SEM) of Gluconacetobacter xylinus, BC nanofibrillar network and schematic

description of the formation of bacterial cellulose.Reproduced with permission from [9].

Figure 2. Images of a laboratory static culture (with a BC membrane well noticeable in air/culture medium interface) and a

purified BC wet membrane produced in static conditions.BC: Bacterial cellulose.

Do bacterial cellulose membranes have potential in drug-delivery systems?

Expert Opin. Drug Deliv. (2014) 11(7) 3

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of high-quality membranes for audio headphones [4,26] andthe use as an additive to produce high-strength paper [7].The properties of BC, mentioned above, such as the high

water-retention capacity, mechanical strength and biocompat-ibility; encouraged also the development of several productsfor biomedical applications, especially as wound dressing [33],temporary skin substitutes [33] and vascular implants [8,43].Biofill�, a temporary human skin substitute for second- andthird-degree burns [16], and Nexfill�, a BC dry bandage forburns and wounds [27], are commercial examples of BC basedproducts.Furthermore, the extremely favorable BC mechanical

properties, biocompatibility, in situ moldability and porosity(that favors cell proliferation), are ideal to explore BC alsoas scaffold for tissue engineering, namely artificial blood ves-sels [16,44], artificial cornea [45], heart valve prosthesis [46], arti-ficial bone [47] and artificial cartilage [48,49]. In a similar vein,BC has also been described as an excellent non-allergic bioma-terial for the cosmetic industry where it can be employed asfacial masks for the treatment of dry skin [50], in the formula-tion of natural facial scrub [51] or as a structuring agent inpersonal cleansing compositions [52].Native BC membranes are likewise promising nanostruc-

tured drug-release systems, as will be discussed more in detailbelow, because of the straightforwardness and effectiveness ofpreparation of the drug-loaded BC membranes and the factthat they are only composed of a single layer. Their abilityto absorb exudates and to adhere to irregular skin surfaces,along with their conformability, are additional crucial issuesfor several clinical situations.Apart from the direct applications mentioned above, in

recent years, there has been a surge of research in the

development of nanocomposite materials based on BC thattry to explore its unique properties (particularly the nanomet-ric dimensions and nanostructured network) in novel func-tional materials. The exploitation of these domains is out ofthe scope of the present appraisal, but an excellent overviewof them can be taken from some recent revisions [20,29-32],with only a brief and illustrative highlight to the nanocompo-sites with proteins [53-66], hydroxyapatite [67-75] and silvernanoparticles [76-96] due to their high potential for biomedicalapplications (the former two) and antimicrobial materials (thelatter).

4. BC on modified drug-delivery systems

BC has been used in several systems for drug delivery assuch [97-105] or after some sort of physical [106,107] or chemicalmodification or else in the form of nanocomposite materialswith diverse polymeric matrices [108-114]. Furthermore, thesesystems have been mainly tested in in vitro transdermaldrug delivery, oral drug delivery and tissue engineering/regeneration.

4.1 Pure BC applications4.1.1 Applications in transdermal drug-delivery

systemsThe use of BC membranes for the transdermal delivery of aseries of drugs, namely lidocaine [97,98], ibuprophen [98],caffeine [99] and diclofenac [100], has been systematically stud-ied by the group of Freire and Silvestre. In all cases, after par-tial removal of its water content the BC membranes wereloaded by absorption of a solution of the selected drug, con-taining a few percent of glycerol, followed by oven drying ofthe solvent. The addition of glycerol played an importantrole specially due to its plasticizing effect, turning the mem-branes more flexible and suitable for dermal application andalso to facilitate their rehydration/swelling. Furthermore,glycerol is also known as humectant and plasticizer of the stra-tum cornea, having potentially a favorable influence on epi-dermal penetration of the drugs. The obtained membranesare very homogeneous and either white or semitransparentas illustrated in Figure 3A for a BC sample loadedwith diclofenac.

Scanning electron microscopy (SEM) analysis of the pureBC and BC loaded with the various drugs demonstratedthat these are uniformly distributed in the surface of the mem-brane (Figure 3B), as no aggregates are formed. Furthermore,SEM analysis also revealed that in the cross-section the spacesare filled due to the presence of the drugs and glycerol.

The swelling of BC-loaded membranes varied between90% for BC-lidocaine [97,98], up to 1200% for BC-diclofenac[100], passing through 284% for caffeine [99]; these differencesshould be related to different hydrophilic characters ofeach drug.

The drug release was governed in all cases essentially bydiffusion and the maximum release was achieved at the end

A.

B. BC BC-glyc-DCF

Figure 3. A. Visual image of a BC-diclofenac membrane with

a good dermal adherence. B. SEM images of pure BC (left)

and BC loaded with caffeine (right).Reproduced with permission from [100].

BC: Bacterial cellulose; SEM: Scanning electron microscopy.



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of 40, 10 and 20 min for lidocaine, caffeine and diclofenac,respectively [97,99,100].

Finally, all four drugs were tested for in vitro skinpermeation [97-100] and compared with conventional formula-tions (Figure 4). With the exception of ibuprophen, slowerpermeation rates are obtained, when compared to conven-tional formulations, which might represent an advantage forsituations where a long-term release of the drug is required.

BC membranes for wound dressing have also been loadedwith silver sulfadiazine, a common drug used in wound treat-ments [103]. It was demonstrated that after impregnation, themembranes showed antimicrobial activity against Pseudomo-nas aeruginosa, Escherichia coli and Staphylococcus aureus, eval-uated by the disc diffusion method, demonstrating that thesemembranes showed good wound-dressing properties and at

the same time are suitable carriers for the delivery of specificwound treatment drugs as silver sulfadiazine.

Mueller et al. [104] studied the loading and release from BCmembranes of bovine serum albumin (BSA) (as a model forproteins delivery). It was demonstrated once more that pro-tein release was controlled by diffusion. It was also demon-strated that freeze-dried BC had a lower uptake capacity foralbumin than pristine BC, which was proposed to be relatedto changes of the fiber network during freeze drying. Further-more, by using a biologically active protein, luciferase, theauthors demonstrated that the integrity and biological activityof proteins could be retained during the loading andrelease processes.

Very recently, Pavaloiu et al. [105] studied the release of theantibiotic amoxicillin from BC membranes in pH conditions

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Figure 4. Drug permeation profiles across human epidermis for A: lidocaine; B: ibuprophen; C: caffeine; D: diclofenac,

compared with conventional formulations.Reproduced with permission from [97,98].



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aimed at mimicking intestine release. Using experimentaldesign tools they have demonstrated that the key factorsaffecting the flux of the drug were its concentration followedby the glycerol content of the dried membranes. They havealso used cetyl trimethyl ammonium bromide as a commontopical drug-delivery permeation enhancer, but in this caseit did not show any positive impact on the flux of the drug.The pH conditions used were also considered to mimicintestinal release.

4.1.2 Applications in oral drug-delivery systemsIn another drug-release application domain, Amin et al. [101]

reported the use of powdered BC to coat paracetamol tabletsusing a spray-coating technique. Coated tablets drug releasewas controlled in vitro. It was demonstrated that BC formedhigh-quality, uniform soft, flexible and foldable films (with-out addition of any plasticizer) comparable to those of Aqua-coat ECD� (an ethyl cellulose aqueous dispersion [115]). Thein vitro drug-release tests revealed that all films stayed intactfor 0.5 h, showing only a moderate swelling. Drug-releaserate depended on the BC loading and therefore on film thick-ness and was slower than for the uncoated tablets. For the lat-ter, complete release was achieved at the end of 100 min whilefor BC-coated tablets (200 µm film thickness) completerelease was only observed at the end of 200 min.More recently, Huang et al. [102] studied the use of BC

membranes as carriers for the in vitro controlled release of ber-berine (an isoquinoline alkaloid). Apart from transdermalcontrolled-release experiments, the membranes were alsotested in simulated gastric (SGF) and intestinal (SIF) fluids,as well as in acidic and alkaline solutions. The results obtainedshowed that the drug was released at a slower rate in low-pHfluids (as SGF), intermediate rates in alkaline conditions andthe highest ratios were observed with near-neutral conditions(as SIF), with the release curves being controlled by free diffu-sion. The pH-dependent behavior of the release rates is asso-ciated with the swellability of BC at different pH values, asconfirmed by SEM analysis of the membranes, which controlsthe fiber interspaces and therefore the free diffusion rate [102].In conclusion, in most studied systems with pure BC the

controlled release of the tested molecules was controlled bydiffusion, and, therefore, the release rates are only systemati-cally affected by temperature and in a more pronouncedway by pH conditions as this last variable affects drasticallythe swelling of the nanofibers and therefore the porosity ofthe material.The release rates can also be tuned if the porosity of BC is

controlled physically or chemically and also if the hydro-philic/phobic character of the environment is altered.For example, Stoica-Guzun et al. [106] accessed the effect of

electron beam irradiation on BC for transdermal drug deliveryof tetracycline, showing that upon irradiation a considerabledecrease in the diffusion was observed. Similarly,Olyveira et al. [107] have also shown that g-irradiated BCmembranes produced lower diffusion rates than native ones,

most certainly due to a high pore density, while the mainthermal and mechanical properties of BC were unaffected.These two studies demonstrate that the diffusion, which, asshown above, controls the release rates, can be tailored byexposing BC to ionizing radiations, opening a way ofphysically controlling those rates.

4.2 BC nanocomposite material applications4.2.1 Applications in oral drug deliveryAnother strategy used to modulate the controlled drugdelivery is the preparation of nanocomposite materials ofBC and diverse polymeric matrices. One of the nanocompo-site materials that has been studied in more detail is the BC-polyacrylic acid (BC/PAA) hydrogels, in which PAA is pro-duced by electron beam irradiation-initiated polymerization,using different radiation doses [109-111]. The authors demon-strated that the swelling degree of the hydrogels grew withincreasing radiation dose and decreasing ionic strength. Thehydrogels were also shown to be pH sensitive with maximumswelling at pH 7. Swelling rates also increased with tempera-ture from 25 to 50�C.

Those BC/PPA nanocomposite hydrogels were tested aspH-responsive materials for controlled in vitro drug deliveryusing different loadings of BSA as model compound [111].As for pure BC, the morphology and pore size of the materialare tunable by the radiation dose. The swelling behavior ofthese hydrogels was demonstrated to be pH dependent, withvalues lower than 1000% below pH 5, reaching a maximumat pH 7 (above 2000%) and then decreasing down to valuesbetween 1500 and 2000% for pH 10.

The drug-release profiles were also controlled using sequen-tially a SGF for 2 h and then a SIF, both without enzymes. Itwas observed that the release in SGF was much slower and atthe end of 2 h only around 15% of BSA was released. On thecontrary, in SIF, the release rate was considerably higher butdecreased with the increasing radiation dose. For the lowestradiation doses a complete release was achieved at the end of8 h, whereas for the highest doses it took 13 -- 14 h.

The different release rates in SGF and SIG are a clear resultof the effect of pH over the swelling rate of the materials, anddemonstrate the pH-responsive behavior of the materialtoward drug delivery, which is remarkably similar to thatreported above for native BC membranes.

The use of BC composites with molecularly imprintedpolymeric (MIP) matrices has been studied by Bodhibukkanaet al. [116] for the enantioselective transdermal delivery of race-mic propranolol. MIP matrices with specific binding siteswere obtained by in situ copolymerization of methacrylicacid with ethylene glycol dimethacrylate as a cross-linker, inthe presence of R- or S-propranolol as the template moleculesand the latter was subsequently extracted. Although selectivetransport of S-propranolol through the MIP composite mem-brane was obtained, this was mostly due to the cellulose mem-brane with some ancillary contributory effect from the MIPlayer. Enantioselectivity in the transport of propranolol



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prodrug enantiomers was found, suggesting that the shapeand functional groups orientation, which are similar to thatof the print molecule, were essential for enantiomeric recogni-tion of the MIP composite membrane. The enantioselectivityof S-MIP membranes was also shown when the release ofpropranolol enantiomers was studied in vitro using rat skin.

More recently, Stroescu et al. have reported the use of poly(vinyl alcohol)-BC mono- and multilayer films for the con-trolled delivery of sorbic acid [108] and vanillin [112] (as a anti-microbial ingredient), demonstrating once more that therelease rate is controlled by diffusion.

In a different vein, Pandey et al. [117] used solubilized anddispersed BC to prepare a superabsorbent BC/polyacrylamidecross-linked hydrogels under microwave irradiation. Theobtained nanocomposite hydrogels showed a swelling behav-ior with maximum swelling at pH 7, and a much higher swell-ing rate (~2300 -- 2500%) for hydrogels prepared withdissolved BC than that reported for those prepared with BCnanofibers (~900%). Furthermore, the materials preparedusing solubilized BC also showed higher porosity, drug-loading efficiency and release.

4.2.2 Applications in tissue-engineering drug-delivery

systemsBC-based materials have also been tested as drug-deliverysystems in tissue engineering and regeneration. Mori et al.[113] studied the release of antibiotics from a bone cement con-taining BC. It was demonstrated that incorporating celluloseinto the bone cement prevented compression and fracture fra-gility, improved fatigue life and increased antibiotic elution.

Finally, the osteogenic potential of a BC scaffold coatedwith bone morphogenetic protein-2 (BMP-2) has been inves-tigated as a localized delivery system to increase the local con-centration of cytokines for tissue engineering [114]. It wasdemonstrated that BC had a good biocompatibility andinduced differentiation of mouse fibroblast-like C2C12 cellsinto osteoblasts in the presence of BMP-2 in vitro. In addi-tion, in vivo subcutaneous implantation studies revealed thatBC scaffolds carrying BMP-2 showed more bone formationand higher calcium concentration than the BC scaffolds aloneat 2 and 4 weeks, respectively, demonstrating that BC is agood localized delivery system for BMPs and would be apotential candidate in bone tissue engineering.

5. Conclusion

The above-made overview clearly demonstrated that BCshows several unique properties (as water-holding capacity,mechanical strength among others, arising from its three-dimensional nanofibrillar network) that impart it with ahigh potential in a wide range of applications, among whichthe biomedical area and drug delivery in particular deservespecial attention. This revision clearly shows that as far asdrug delivery is concerned BC demonstrated to have excellentproperties, both in dermal and in oral delivery system

applications, which can be further tailored by consideringBC physical treatments or its use in composite materials.

6. Expert opinion

The current appraisal demonstrated that BC is a natural mate-rial, produced by non-pathogenic bacteria with high potentialfor application in drug-delivery systems, both for transdermal,oral and tissue-engineering applications, apart from other bio-medical applications mentioned above. However, due to thelimited number of studies available in the literature (only18 studies were reported [97-114], of which 9 dealt with pureBC [97-105], 2 with physically modified BC [106,107] and7 with nanocomposite materials with diverse matrices[108-114]), there is still plenty of scope to proceed with theinvestigation in this domain in a more systematic way. Theinterest in developing these studies is further reinforced bythe demonstrated general biocompatibility and even the tradi-tional use as food that eliminates almost completely any riskof adverse effects, as recently demonstrated for transdermalapplications [39].

In several cases, and particularly for oral delivery systemapplications, it will be beneficial to study in parallel thedrug-delivery behavior of BC produced under static condi-tions (where membranes need to be cut into small fractionssuitable for oral intake) and under agitated conditions (whereBC can be attractively available in sphere-like forms of tun-able size), since the microscopic characteristics (e.g., porosity)of BC are not exactly the same. Furthermore, this comparisonof the drug-delivery behavior of BC produced under staticand agitated conditions should be considered not only forpure BC applications but also when other physical/chemicalmodifications take place.

Provided that, as demonstrated in most studies reportedabove, drug-delivery rates were controlled by diffusion andthe tailoring of release rates will be much dependent on thesearch for additional physical treatments, or chemical modifi-cation/compounding approaches that would enable a highercontrol over the diffusion, and particularly in a responsiveway against external/body stimuli. In this vein some pH-responsive materials were already mentioned above [111], butit would be extremely interesting to have materials wherethe drug release would for example be triggered by body tem-perature raise above healthy values to prevent fever effects.

The production of BC-based nanocomposites for drugdelivery has been tested with several polymeric matrices,namely PAA [111], polyvinyl alcohol [108,112], polyacryl-amide [117] and molecularly imprinted polymers [116]; how-ever, the realm of polymers is so vast that many othersshould be tested, obviously taking into considerations specificinteractions with target drugs that might modulate theirrelease. Here, polyelectrolites can be of particular interest fortheir interaction with charged drugs. Ultimately, the affinityof the drugs toward the material could in the case of compo-sites be further tuned using molecular imprinted polymeric



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matrices designed on demand for each specific drug and nota-bly for enantiomeric differentiation.Finally, the direct chemical modification of BC nanofiber

surface (instead of production of nanocomposite materials)has not been attempted before. This approach would alsocontribute to tune the hydrophilic character and thereforethe drug’s affinity toward the fiber surface and therefore thedelivery behavior, by appending simple chemical groups, oreven polymers following sleeving approaches (e.g., [118]). Ina more sophisticated way this approach can also be used tointroduce groups with enhanced selectivity for specific drugsas, for example, cyclodextrines (e.g., [119]) that will tune theabsorption and the release of the drug in a much moreselective way.Although to the moment most studies were centered on

dermal and oral delivery systems, the application of BCshould also be more studied in other areas, particularly as acomplement of other BC applications, that is, to conjugatethe potential of BC in wound healing and tissue repair/

regeneration with the in situ controlled release of specificdrugs, but also in tissue engineering where these materialsshow high potential.

Declaration of interest

The authors were supported by FCT (Fundacao para aCiencia e Tecnologia) and POPH/FSE for funding theAssociate Laboratory CICECO (PEst-C/CTM/LA0011/2013, FCOMP-01-0124-FEDER-037271) and the projectsEXPL/CTM-ENE/0548/2012 (FCOMP-01-0124-FEDER-027691), EXPL/CTM-POL/1802/2013 (FCOMP-01-0124-FEDER-041484). C.S.R. Freire was supported by FCT/MCTES for a research contract under the Program“Investigador FCT 2012.” The authors have no other relevantaffiliations or financial involvement with any organization orentity with a financial interest in or financial conflict withthe subject matter or materials discussed in the manuscriptapart from those disclosed.

BibliographyPapers of special note have been highlighted as

either of interest (�) or of considerable interest(��) to readers.

1. Klemm D, Heublein B, Fink H-P, et al.

Cellulose: fascinating biopolymer and

sustainable raw material. Angew Chem

Int Ed Engl 2005;44(22):3358-93

2. Gandini A. Polymers from renewable

resources: a challenge for the future of

macromolecular materials.

Macromolecules 2008;41(24):9491-504

3. Huber T, Mussig J, Curnow O, et al.

A critical review of all-cellulose

composites. J Mater Sci

2011;47(3):1171-86

4. Chawla PR, Bajaj IB, Survase SA, et al.

Microbial cellulose: fermentative

production and applications.

Food Technol Biotecnol

2009;47(2):107-24

5. Brown AJ. XLIII-On an acetic ferment

which form cellulose. J Chem Soc

1886;49:432-9

6. Brown AJ. XIX.----The chemical action of

pure cultivations of bacterium aceti.

J Chem Soc 1886;49:172-87

7. Iguchi M, Yamanaka S, Budhiono A.

Bacterial cellulose ---- a masterpiece of

nature’s arts. J Mater Sci

2000;35(2):261-70

. Review dealing with the potential of

bacterial cellulose.

8. Klemm D, Schumann D, Udhardt U,

et al. Bacterial synthesized cellulose ----

artificial blood vessels for microsurgery.

Prog Polym Sci 2001;26(9):1561-603

9. Shi Z, Zhang Y, Phillips GO, et al.

Utilization of bacterial cellulose in food.

Food Hydrocoll 2014;35:539-45

10. Trovatti E, Serafim LS, Freire CSR,

et al. Gluconacetobacter sacchari:

an efficient bacterial cellulose cell-factory.

Carbohydr Polym 2011;86(3):1417-20

11. Gomes FP, Silva NHCS, Trovatti E,

et al. Production of bacterial cellulose by

Gluconacetobacter sacchari using dry

olive mill residue. Biomass Bioenergy

2013;55:205-11

12. Hestrin S, Schramm M. Synthesis of

cellulose by Acetobacter xylinum II.

Preparation of freeze-dried cells capable

of polymerizing glucose to cellulose.

Biochem J 1954;58:345-52

13. Nge TT, Sugiyama J, Bulone V.

Bacterial cellulose-based biomimetic

composites. In: Elnashar M, editor.

Biopolymers. Sciyo, Rijeka;

2010. p. 345-68

14. Helenius G, Backdahl H, Bodin A, et al.

In vivo biocompatibility of bacterial

cellulose. J Biomed Mater Res A

2006;76(2):431-8

15. Jonas R, Farah LF. Production and

application of microbial cellulose.

Polym Degrad Stab 1998;59(1-3):101-6

16. Klemm D, Schumann D, Udhardt U,

et al. Bacterial synthesized cellulose ----

artificial blood vessels for microsurgery.

Prog Polym Sci 2001;26(9):1561-603

17. Klemm D, Kramer F, Moritz S, et al.

Nanocelluloses: a new family of nature-

based materials. Angew Chem Int

Ed Engl 2011;50(24):5438-66

18. Sani A, Dahman Y. Improvements in the

production of bacterial synthesized

biocellulose nanofibres using different

culture methods. J Chem

Technol Biotechnol 2010;85:151-64

19. Watanabe K, Tabuchi M, Morinaga Y,

et al. Structural features and properties of

bacterial cellulose produced in agitated

culture. Cellulose 1998;5(3):187-200

20. Fu L, Zhang J, Yang G. Present status

and applications of bacterial cellulose-

based materials for skin tissue repair.

Carbohydr Polym 2013;92:1432-42

. Review of bacterial cellulose

applications in skin tissue repair.

21. Fu L, Zhang Y, Li C, et al. Skin tissue

repair materials from bacterial cellulose

by a multilayer fermentation method.

J Mater Chem 2012;22:12349-57

22. White DG, Brown RM. Prospects for

the commercialization of the biosynthesis

of microbial cellulose. In: Schuerch C,

editor. Cellulose and wood-chemistry and

technology. John Wiley and Sons, New

York; 1989. p. 573-90

23. Czaja W, Romanovicz D, Brown RM.

Structural investigations of microbial

cellulose produced in stationary and

agitated culture. Cellulose

2004;11(3-4):403-11



Exp

ert O

pin.

Dru

g D

eliv

. Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

itaet

Zue

rich

on

06/0

3/14

For

pers

onal

use

onl

y.

http://www.ncbi.nlm.nih.gov/pubmed/15861454?dopt=Abstract





















24. Cheng K-C, Catchmark JM, Demirci A.

Enhanced production of bacterial

cellulose by using a biofilm reactor and

its material property analysis. J Biol Eng

2009;3:12

25. Hu Y, Catchmark JM. Formation and

characterization of spherelike bacterial

cellulose particles produced by

Acetobacter xylinum JCM 9730 strain.

Biomacromolecules 2010;11(7):1727-34

26. Kalia S, Dufresne A, Cherian BM, et al.

Cellulose-based bio- and nanocomposites:

a review. Int J Polym Sci

2011;2011:1-35

27. Pecoraro E, Manzani D, Messaddeq Y,

et al. Bacterial cellulose from

glucanacetobacter xylinus: preparation,

properties and applications. In:

Gandini A, editor. Monomers, polymers

and composited from renewable

resources. Elsevier, Amsterdam;

2008. p. 369-74

28. Klemm D, Schumann D, Kramer F,

et al. Nanocelluloses as innovative

polymers in research and application.

Adv Polym Sci 2006;205:49-96

29. Chen P, Cho SY, Jin H-J. Modification

and applications of bacterial celluloses in

polymer science. Macromol Res

2010;18:309-20

. Review of bacterial

cellulose applications.

30. Shah N, Ul-Islam M, Khattak WA, et al.

Overview of bacterial cellulose

composites: a multipurpose advanced

material. Carbohydr Polym

2013;98:1585-98



31. Hu W, Chen S, Yang J, et al.

Functionalized bacterial cellulose

derivatives and nanocomposites.

Carbohydr Polym 2014;101:1043-60



32. Figueiredo ARP, Vilela C,

Pascoal Neto C, et al. Bacterial cellulose

based nanocomposites: a roadmap for

innovative materials. In: Kumar V,

editor. Nanocellulose/polymer

nanocomposites: from fundamental

to applications. John Wiley and Sons,

New York; in press



33. Czaja W, Krystynowicz A, Bielecki S,

et al. Microbial cellulose-the natural

power to heal wounds. Biomaterials

2006;27(2):145-51



34. Siro I, Plackett D. Microfibrillated

cellulose and new nanocomposite

materials: a review. Cellulose

2010;17(3):459-94

35. Yamanaka S, Watanabe K, Kitamura N,

et al. The structure and mechanical

properties of sheets prepared from

bacterial cellulose. J Mater Sci

1989;24(9):3141-5

36. Shi Z, Zang S, Jiang F, et al. In situ

nano-assembly of bacterial

cellulose--polyaniline composites.

RSC Adv 2012;2(3):1040-6

37. Jeong SI, Lee SE, Yang H, et al.

Toxicologic evaluation of bacterial

synthesized cellulose in endothelial cells

and animals. Mol Cell Toxicol

2010;6:373-80

38. Lina F, Yue Z, Jin Z, et al. Bacterial

cellulose for skin repair materials. In:

Fazel-Rezai P, editor. Biomedical

engineering - frontiers and challenges.

Intech, Rijeka; 2011. p. 249-74

39. Almeida IF, Pereira T, Silva NHCS,

et al. Bacterial cellulose membranes as

drug delivery systems: an in vivo skin

compatibility study. Eur J

Pharm Biopharm 2014;106:264-9

. Paper dealing with the skin

compatibility of bacterial cellulose.

40. Wu S-C, Lia Y-K. Application of

bacterial cellulose pellets in enzyme

immobilization. J Mol Catal B Enzym

2008;54:103-8

41. Nguyen DN, Ton NMN, Le VVM.

Optimization of Saccharomyces cerevisiae

immobilization in bacterial cellulose by

“adsorption- incubation” method.

Int Food Res J 2009;16:59-64

42. Ton NMN, Le VVM. Application of

immobilized yeast in bacterial cellulose to

the repeated batch fermentation in

wine-making. Int Food Res J

2011;18(3):983-7

43. Backdahl H, Risberg B, Gatenholm P.

Observations on bacterial cellulose tube

formation for application as vascular

graft. Mater Sci Eng C 2011;31(1):14-21

44. Wan Y, Gao C, Han M, et al.

Preparation and characterization of

bacterial cellulose/heparin hybrid

nanofiber for potential vascular tissue

engineering scaffolds.

Polym Adv Technol 2011;22:2643-8

45. Wang J, Gao C, Zhang Y, et al.

Preparation and in vitro characterization

of BC/PVA hydrogel composite for its

potential use as artificial cornea

biomaterial. Mater Sci Eng C

2010;30:214-18

46. Millon LE, Wan WK. The polyvinyl

alcohol-bacterial cellulose system as a

new nanocomposite for biomedical

applications. J Biomed Mater Res B

2006;79(2):245-53

47. Zimmermann KA, LeBlanc JM,

Sheets KT, et al. Biomimetic design of a

bacterial cellulose/hydroxyapatite

nanocomposite for bone healing

applications. Mater Sci Eng C

2011;31:43-9

48. Svensson A, Nicklasson E, Panilaitis B,

et al. Bacterial cellulose as a potential

scaffold for tissue engineering of

cartilage. Biomaterials 2005;26:419-31

49. Nimeskern L, Avila HM, Sundberg J,

et al. Mechanical evaluation of bacterial

nanocellulose as an implant material for

ear cartilage replacement. J Mech Behav

Biomed Mater 2013;22:12-21

50. Amnuaikit T, Chusuit T, Raknam P,

et al. Effects of a cellulose mask

synthesized by a bacterium on facial skin

characteristics and user satisfaction.

Med Devices (Auckl) 2011;4:77-81

51. Hasan N, Biak DRA, Kamarudin S.

Application of bacterial cellulose (BC) in

natural facial scrub. Int J Adv Sci Eng

Inf Technol 2012;2:1-4

52. Heath, Benjamin Parker, Coffindaffer

TW, Kyte, Kenneth Eugene, Smith

Edward Dewey, McConaughy SD.

Personal cleansing compositions

comprising bacterial cellulose network

and cationic polymer. US 8097574;

2010

53. Wiegand C, Elsner P, Hipler U-C, et al.

Protease and ROS activities influenced

by a composite of bacterial cellulose and

collagen type I in vitro. Cellulose

2006;13(6):689-96

54. Luo H, Xiong G, Huang Y, et al.

Preparation and characterization of a

novel COL/BC composite for potential

tissue engineering scaffolds.

Mater Chem Phys 2008;110(2-3):193-6

55. Zhijiang C, Guang Y. Bacterial cellulose/

collagen composite: characterization and



Exp

ert O

pin.

Dru

g D

eliv

. Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

itaet

Zue

rich

on

06/0

3/14

For

pers

onal

use

onl

y.

































first evaluation of cytocompatibility.

J Appl Polym Sci 2011;120:2938-44

56. Saska S, Teixeira LN,

Tambasco de Oliveira P, et al. Bacterial

cellulose-collagen nanocomposite for

bone tissue engineering. J Mater Chem

2012;22(41):22102

57. Brown EE, Zhang J, Laborie M-PG.

Never-dried bacterial cellulose/fibrin

composites: preparation, morphology and

mechanical properties. Cellulose

2011;18:631-41

58. Lin S-B, Hsu C-P, Chen L-C, et al.

Adding enzymatically modified gelatin to

enhance the rehydration abilities and

mechanical properties of bacterial

cellulose. Food Hydrocoll

2009;23(8):2195-203

59. Brown EE, Laborie M-PG, Zhang J.

Glutaraldehyde treatment of bacterial

cellulose/fibrin composites: impact on

morphology, tensile and viscoelastic

properties. Cellulose 2011;19(1):127-37

60. Wang J, Wan YZ, Luo HL, et al.

Immobilization of gelatin on bacterial

cellulose nanofibers surface via

crosslinking technique. Mater Sci Eng C

2012;32(3):536-41

61. Chang S-T, Chen L-C, Lin S-B, et al.

Nano-biomaterials application:

morphology and physical properties of

bacterial cellulose/gelatin composites via

crosslinking. Food Hydrocoll

2012;27(1):137-44

62. Taokaew S, Seetabhawang S, Siripong P,

et al. Biosynthesis and characterization of

nanocellulose-gelatin films.

Materials (Basel) 2013;6(3):782-94

63. Choi Y, Cho SY, Heo S, et al. Enhanced

mechanical properties of silk fibroin-

based composite plates for fractured bone

healing. Fibers Polym 2013;14(2):266-70

64. Hu Y, Catchmark JM. Integration of

cellulases into bacterial cellulose: toward

bioabsorbable cellulose composites.

J Biomed Mater Res B Appl Biomater

2011;97(1):114-23

65. Zhu H, Jia S, Yang H, et al.

Characterization of bacteriostatic sausage

casing: A composite of bacterial cellulose

embedded with "polylysine.

Food Sci Biotechnol 2010;19(6):1479-84

66. Hu Y, Catchmark JM. In vitro

biodegradability and mechanical

properties of bioabsorbable bacterial

cellulose incorporating cellulases.

Acta Biomater 2011;7(7):2835-45

67. Khripunov AK, Baklagina YG,

Sinyaev VA, et al. Investigation of

nanocomposites based on hydrated

calcium phosphates and cellulose

Acetobacter xylinum. Glass Phys Chem

2008;34:192-200

68. Grande CJ, Torres FG, Gomez CM,

et al. Nanocomposites of bacterial

cellulose/hydroxyapatite for biomedical

applications. Acta Biomater

2009;5:1605-15

69. Shi S, Chen S, Zhang X, et al.

Biomimetic mineralization synthesis of

calcium-deficient carbonate-containing

hydroxyapatite in a three-dimensional

network of bacterial cellulose. J Chem

Technol Biotechnol 2009;84:285-90

70. Wan YZ, Gao C, Luo HL, et al. Early

growth of nano-sized calcium phosphate

on phosphorylated bacterial cellulose

nanofibers. J Nanosci Nanotechnol

2009;9:6494-500

71. Romanov DP, Baklagina YG,

Gubanova GN, et al. Formation of

organic-inorganic composite materials

based on cellulose Acetobacter xylinum

and calcium phosphates for medical

applications. Glass Phys Chem

2010;36:484-93

72. Yin N, Chen S, Ouyang Y, et al.

Biomimetic mineralization synthesis of

hydroxyapatite bacterial cellulose

nanocomposites. Prog Nat Sci Mater Int

2011;21:472-7

73. Hammonds RL, Harrison MS,

Cravanas TC, et al. Biomimetic

hydroxyapatite powder from a bacterial

cellulose scaffold. Cellulose

2012;19:1923-32

74. Tolmachev DA, Lukasheva NV.

Interactions binding mineral and organic

phases in nanocomposites based on

bacterial cellulose and calcium

phosphates. Langmuir 2012;28:13473-84

75. Fan X, Zhang T, Zhao Z, et al.

Preparation and characterization of

bacterial cellulose microfiber/goat bone

apatite composites for bone repair.

J Appl Polym Sci 2013;129:595-603

76. Marques PAAP, Nogueira HIS,

Pinto RJB, et al. Silver-bacterial cellulosic

sponges as active SERS substrates.

J Raman Spectrosc 2008;39:439-43

77. Barud HS, Barrios C, Regiani T, et al.

Self-supported silver nanoparticles

containing bacterial cellulose membranes.

Mater Sci Eng C 2008;28:515-18

78. Maneerung T, Tokura S, Rujiravanit R.

Impregnation of silver nanoparticles into

bacterial cellulose for antimicrobial

wound dressing. Carbohydr Polym

2008;72:43-51

79. Klechkovskaya VV, Volkov VV,

Shtykova EV, et al. Network model of

Acetobacter xylinum cellulose intercalated

by drug nanoparticles. In: Giersig M,

Khomutov GB, editors. Nanomaterials

for applications in medicine and biology.

Springer, Dordrecht; 2008. p. 165-77

80. Sun D, Yang J, Li J, et al. Preparation

and antibacterial capacity of artificial skin

loaded with nanoparticles silver using

bacterial cellulose. Sheng Wu Yi Xue

Gong Cheng Xue Za Zhi

2009;26:1034-8

81. Ifuku S, Tsuji M, Morimoto M, et al.

Synthesis of silver nanoparticles

templated by TEMPO-mediated oxidized

bacterial cellulose nanofibers.

Biomacromolecules 2009;10:2714-17

82. Jung R, Kim Y, Kim H-S, et al.

Antimicrobial properties of hydrated

cellulose membranes with silver

nanoparticles. J Biomater Sci Polym Ed

2009;20:311-24

83. Volkov V V, Klechkovskaya V V,

Shtykova E V, et al. Determination of

the size and phase composition of silver

nanoparticles in a gel film of bacterial

cellulose by small-angle X-ray scattering,

electron diffraction, and electron

microscopy. Crystallogr Rep

2009;54:169-73

84. De Santa Maria LC, Santos ALC,

Oliveira PC, et al. Synthesis and

characterization of silver nanoparticles

impregnated into bacterial cellulose.

Mater Lett 2009;63:797-9

85. Pinto RJB, Marques PAAP,

Pascoal Neto C, et al. Antibacterial

activity of nanocomposites of silver and

bacterial or vegetable cellulosic fibers.

Acta Biomater 2009;5:2279-89

86. Sureshkumar M, Siswanto DY, Lee C-K.

Magnetic antimicrobial nanocomposite

based on bacterial cellulose and silver

nanoparticles. J Mater Chem

2010;20:6948-55

87. Maria LCS, Santos ALC, Oliveira PC,

et al. Preparation and antibacterial

activity of silver nanoparticles

impregnated in bacterial cellulose.

Polim Cien Tecnol 2010;20:72-7



Exp

ert O

pin.

Dru

g D

eliv

. Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

itaet

Zue

rich

on

06/0

3/14

For

pers

onal

use

onl

y.

































88. Wang W, Li H-Y, Zhang D-W, et al.

Fabrication of bienzymatic glucose

biosensor based on novel gold

nanoparticles-bacteria cellulose nanofibers

nanocomposite. Electroanalysis

2010;22:2543-50

89. Wang W, Zhang T-J, Zhang D-W, et al.

Amperometric hydrogen peroxide

biosensor based on the immobilization of

heme proteins on gold nanoparticles-

bacteria cellulose nanofibers

nanocomposite. Talanta 2011;84:71-7

90. Yang G, Xie J, Hong F, et al.

Antimicrobial activity of silver

nanoparticle impregnated bacterial

cellulose membrane: effect of

fermentation carbon sources of bacterial

cellulose. Carbohydr Polym

2012;87:839-45

91. Yang G, Xie J, Deng Y, et al.

Hydrothermal synthesis of bacterial

cellulose/AgNPs composite: a “green”

route for antibacterial application.


92. Liu C, Yang D, Wang Y, et al.

Fabrication of antimicrobial bacterial

cellulose-Ag/AgCl nanocomposite using

bacteria as versatile biofactory.

J Nanopart Res 2012;14:1084-95

93. Berndt S, Wesarg F, Wiegand C, et al.

Antimicrobial porous hybrids consisting

of bacterial nanocellulose and silver

nanoparticles. Cellulose 2013;20:771-83

94. Zhang X, Fang Y, Chen W. Preparation

of silver/bacterial cellulose composite

membrane and study on its antimicrobial

activity. Syn React Inorg Met

2013;43:907-13

95. Dobre ML, Stoica-Guzun A.

Antimicrobial Ag-polyvinyl alcohol-

bacterial cellulose composite films.

J Biobased Mater Bioenergy

2013;7:157-62

96. Kim B, Choi Y, Cho SY, et al. Silver

nanowire catalysts on carbon nanotubes-

incorporated bacterial cellulose

membrane electrodes for oxygen

reduction reaction.

J Nanosci Nanotechnol

2013;13(11):7454-8

97. Trovatti E, Silva NHCS, Duarte IF,

et al. Biocellulose membranes as supports

for dermal release of lidocaine.


.. Paper dealing with the use of bacterial

cellulose on controlled modified drug

delivery systems.

98. Trovatti E, Freire CSR, Pinto PC, et al.

Bacterial cellulose membranes applied in

topical and transdermal delivery of

lidocaine hydrochloride and ibuprofen:

in vitro diffusion studies. Int J Pharm

2012;435(1):83-7



delivery systems.

99. Silva NHCS, Drumond I, Almeida IF,

et al. Topical caffeine delivery using

biocellulose membranes: a potential

innovative system for cellulite treatment.

Cellulose 2014;21:665-74



delivery systems.

100. Silva NHCS, Rodrigues AF, Almeida IF,

et al. Bacterial cellulose membranes as

transdermal delivery systems for

diclofenac: in vitro dissolution and

permeation studies. Carbohydr Polym

2014;106:264-9



delivery systems.

101. Amin MCIM, Abadi AG, Ahmad N,

et al. Bacterial cellulose film coating as

drug delivery system: physicochemical,

thermal and drug release properties.

Sains Malaysiana 2012;41(5):561-8



delivery systems.

102. Huang L, Chen X, Nguyen TX, et al.

Nano-cellulose 3D-networks as

controlled-release drug carriers. J Mater

Chem B 2013;1(23):2976-84



delivery systems.

103. Luan J, Wu J, Zheng Y, et al.

Impregnation of silver sulfadiazine into

bacterial cellulose for antimicrobial and

biocompatible wound dressing.

Biomed Mater 2012;7:ID065006



delivery systems.

104. Mueller A, Ni Z, Hessler N, et al. The

biopolymer bacterial nanocellulose as

drug delivery system: investigation of

drug loading and release using the model

protein albumin. J Pharm Sci

2013;102(2):579-92



delivery systems.

105. Pavaloiu R-D, Stoica A, Stroescu M,

et al. Controlled release of amoxicillin

from bacterial cellulose membranes.

Cent Eur J Chem 2014;12:962-7



delivery systems.

106. Stoica-Guzun A, Stroescu M, Tache F,

et al. Effect of electron beam irradiation

on bacterial cellulose membranes used as

transdermal drug delivery systems.

Nucl Instrum Meth Phys Res B

2007;265(1):434-8



delivery systems.

107. De Olyveira GM, Manzine Costa LM,

Basmaji P. Physically modified bacterial

cellulose as alternative routes for

transdermal drug delivery. J Biomater

Tissue Eng 2013;3(2):227-32



delivery systems.

108. Jipa IM, Stoica-Guzun A, Stroescu M.

Controlled release of sorbic acid from

bacterial cellulose based mono and

multilayer antimicrobial films.

LWT-Food Sci Technol

2012;47(2):400-6



delivery systems.

109. Halib N, Amin MCIM, Ahmad I, et al.

Swelling of bacterial cellulose-acrylic acid

hydrogels: sensitivity towards external

stimuli. Sains Malaysiana

2009;38(5):785-91

110. Halib N, Amin MCIM, Ahmad I.

Unique stimuli responsive characteristics

of electron beam synthesized bacterial

cellulose/acrylic acid composite. J Appl

Polym Sci 2010;116:2920-9

111. Amin MCIM, Ahmad N, Halib N, et al.

Synthesis and characterization of thermo-

and pH-responsive bacterial cellulose/

acrylic acid hydrogels for drug delivery.




delivery systems.

112. Stroescu M, Stoica-Guzun A, Jipa IM.

Vanillin release from poly(vinyl alcohol)-

bacterial cellulose mono and multilayer

films. J Food Eng 2013;114(2):153-7



delivery systems.



Exp

ert O

pin.

Dru

g D

eliv

. Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

itaet

Zue

rich

on

06/0

3/14

For

pers

onal

use

onl

y.



































113. Mori R, Nakai T, Enomoto K, et al.

Increased antibiotic release from a bone

cement containing bacterial cellulose.

Clin Orthop Relat Res 2011;469(2):600-6



delivery systems.

114. Shi Q, Li Y, Sun J, et al. The

osteogenesis of bacterial cellulose scaffold

loaded with bone morphogenetic

protein-2. Biomaterials

2012;33(28):6644-9



delivery systems.

115. FMC Biopolymer: Aquacoat�. Available

from: http://www.fmcbiopolymer.com/

Pharmaceutical/Products/Aquacoat.aspx

[Accessed on April 2014]

116. Bodhibukkana C, Srichana T,

Kaewnopparat S, et al. Composite

membrane of bacterially-derived cellulose

and molecularly imprinted polymer for

use as a transdermal enantioselective

controlled-release system of racemic

propranolol. J Control Release

2006;113(1):43-56



delivery systems.

117. Pandey M, Amin MCIM, Ahmad N,

et al. Rapid synthesis of superabsorbent

smart-swelling bacterial cellulose/

acrylamide-based hydrogels for drug

delivery. Int J Polym Sci

2013:ID 905471



delivery systems.

118. Lacerda PSS, Barros-Timmons AMMV,

Freire CSR, et al. Nanostructured

composites obtained by ATRP

SLEEVING of bacterial cellulose

nanofibers with acrylate polymers.


119. Dong C, Qian L-Y, Zhao G-L, et al.

Preparation of antimicrobial cellulose

fibers by grafting beta-cyclodextrin and

inclusion with antibiotics. Mater Lett

2014;124:181-3

AffiliationArmando JD Silvestre†1 PhD,

Carmen SR Freire*2 PhD & Carlos P Neto3 PhD†,*Authors for correspondence1Associate Professor,

University of Aveiro, CICECO and

Department of Chemistry,

3810-193 Aveiro, Portugal

Tel: +351 234 370 711;

E-mail: [email protected] Researcher,




Tel: +351 234 370 711;

E-mail: [email protected] Professor,






Exp

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Documents

Do bacterial cellulose membranes have potential in drug-delivery systems?