Abstract
Although bacterial nanocellulose (BNC), a natural nanostructured biopolymer network, offers unique material characteristics, the number of drug-loaded BNC-based carriers in clinical trials or on the market is still low. This report provides an overview of aspects still limiting the broad application of BNC as drug-delivery system and the challenges for its future applications. Continuous large-scale production, storability, the loading and controlled release of critical drugs, for example, with high molar mass or highly lipophilic character as well as the formulation of long-term release systems will be highlighted. Recent achievements toward promoting the application of BNC as drug-delivery system and overcoming these obstacles will be discussed.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1 Nanocelluloses: a new family of nature-based materials. Angew. Chem. Int. Ed. 50(24), 5438–5466 (2011). •• Provides an overview about modifications and applications of nanocelluloses.
- 2 . Review of cellulose nanocrystals patents: preparation, composites and general applications. Recent. Pat. Nanotech. 6(1), 16–28 (2012).
- 3 . Efficient homogeneous chemical modification of bacterial cellulose in the ionic liquid 1-N-Butyl-3-methylimidazolium chloride. Macromol. Rapid. Comm. 27(19), 1670–1676 (2006).
- 4 Thermal characterization of bacterial cellulose–phosphate composite membranes. J. Therm. Anal. Calorim. 87(3), 815–818 (2007).
- 5 . Nanocellulose in biomedicine: current status and future prospect. Eur. Polym. J. 59, 302–325 (2014).
- 6 . Toxicologic evaluation of bacterial synthesized cellulose in endothelial cells and animals. Mol. Cell. Toxicol. 6(4), 370–377 (2010).
- 7 . In vivo biocompatibility of bacterial cellulose. J. Biomed. Mater. Res. A. 76(2), 431–438 (2006).
- 8 Artificial vascular implants from bacterial cellulose: preliminary results of small arterial substitutes. Cellulose 16(5), 877–885 (2009).
- 9 Bacterial cellulose membranes as drug-delivery systems: an in vivo skin compatibility study. Eur. J. Pharm. Biopharm. 86(3), 332–336 (2014). • Presents a clinical study about the use of bacterial nanocellulose (BNC) for skin applications.
- 10 Frost & Sullivan. Emerging applications of nanocellulose technology. https://store.frost.com/emerging-applications-of-nanocellulose-technology.html.
- 11 . New antimicrobial wound dressing with polyhexanide Suprasorb® X + PHMB, first in vitro and clinical results. Presented at: Annual Congress of the German Society for Wound Healing and Wound Care. Berlin, Germany, 9–10 March 2007.
- 12 . Evaluation of cellulose and polyhexamethylene biguanide (Suprasorb® X+PHMB) in therapy of infected wounds. EWMA J. (Suppl.) 8(2), 54 (2008).
- 13 Bowil Biotech Sp. z o.o. www.bowil.pl.
- 14 Bacterial cellulose membranes as transdermal delivery systems for diclofenac: in vitro dissolution and permeation studies. Carbohyd. Polym. 106, 264–269 (2014).
- 15 Active wound dressings based on bacterial nanocellulose as drug-delivery system for octenidine. Int. J. Pharm. 471(1–2), 45–55 (2014).
- 16 Bacterial cellulose membranes applied in topical and transdermal delivery of lidocaine hydrochloride and ibuprofen: in vitro diffusion studies. Int. J. Pharm. 435(1), 83–87 (2012).
- 17 . Applications of bacterial cellulose in food, cosmetics and drug delivery. Cellulose 23(4), 2291–2314 (2016). •• Presents a summary of drugs incorporated into BNC.
- 18 Antimicrobial functionalization of bacterial nanocellulose by loading with polihexanide and povidone-iodine. J. Mater. Sci. Mater. Med. 26(10), 245 (2015).
- 19 . Biocompatible and mucoadhesive bacterial cellulose-g-poly(acrylic acid) hydrogels for oral protein delivery. Mol. Pharm. 11(11), 4130–4142 (2014).
- 20 The biopolymer bacterial nanocellulose as drug-delivery system: investigation of drug loading and release using the model protein albumin. J. Pharm. Sci. 102(2), 579–592 (2013).
- 21 Laccase immobilization on bacterial nanocellulose membranes: antimicrobial, kinetic and stability properties. Carbohyd. Polym. 145, 1–12 (2016).
- 22 . Novel process for immobilizing an enzyme on a bacterial cellulose membrane through repeated absorption. J. Chem. Technol. Biotechnol. 92(1), 109–114 (2017).
- 23 Fabrication, characterization and evaluation of bacterial cellulose-based capsule shells for oral drug delivery. Cellulose 1–10 (2017).
- 24 . Nano-cellulose 3D-networks as controlled-release drug carriers. J. Mater. Chem. B 1(23), 2976–2984 (2013).
- 25 Applicability of bacterial cellulose as an alternative to paper points in endodontic treatment. Acta Biomater. 9(4), 6116–6122 (2013).
- 26 . Production of biocompatible and antimicrobial bacterial cellulose polymers functionalized by RGDC grafting groups and gentamicin. ACS Appl. Mater. Inter. 6(3), 1439–1446 (2014).
- 27 Nanomaterials from bacterial cellulose for antimicrobial wound dressing. J. Phys. Conf. Ser. 784(1), 012034 (2017).
- 28 Controlled release and antibacterial activity of tetracycline hydrochloride-loaded bacterial cellulose composite membranes. Carbohyd. Polym. 145, 114–120 (2016).
- 29 . pH- and electro-response characteristics of bacterial cellulose nanofiber/sodium alginate hybrid hydrogels for dual controlled drug delivery. RSC Adv. 4(87), 47056–47065 (2014).
- 30 Biocellulose membranes as supports for dermal release of lidocaine. Biomacromolecules 12(11), 4162–4168 (2011).
- 31 . Self-assembly of carrageenin–CaCO3 hybrid microparticles on bacterial cellulose films for doxorubicin sustained delivery. J. Appl. Biomed. 13(3), 239–248 (2015).
- 32 . Loading of bacterial nanocellulose hydrogels with proteins using a high-speed technique. Carbohyd. Polym. 106, 410–413 (2014).
- 33 . Study on the drug loading and release potential of bacterial cellulose. Cell. Chem. Technol. 50(2), 219–223 (2016).
- 34 . Controlled extended octenidine release from a bacterial nanocellulose/poloxamer hybrid system. Eur. J. Pharm. Biopharm. 112, 164–176 (2017). •• First description of BNC for the use as long-term release systems for antiseptics.
- 35 . The characteristics of bacterial nanocellulose gel releasing silk sericin for facial treatment. BMC Biotechnol. 14, 104 (2014).
- 36 . Modified bacterial cellulose scaffolds for localized doxorubicin release in human colorectal HT-29 cells. Colloid. Surface. B 140, 421–429 (2016).
- 37 . Preparation and characterization of 2,3-dialdehyde bacterial cellulose for potential biodegradable tissue engineering scaffolds. Mater. Sci. Eng. C 29(5), 1635–1642 (2009).
- 38 . Functionalized bacterial cellulose derivatives and nanocomposites. Carbohyd. Polym. 101, 1043–1060 (2014).
- 39 . Grafting of thermosensitive poly(N-isopropylacrylamide) from wet bacterial cellulose sheets to improve its swelling-drying ability. Cellulose 24(1), 285–293 (2017).
- 40 . Swelling studies of composite hydrogels based on bacterial cellulose and gelatin. U.P.B. Sci. Bull. Ser. B 77(1), 53–62 (2015).
- 41 . Composite films of poly(vinyl alcohol)–chitosan–bacterial cellulose for drug controlled release. Int. J. Biol. Macromol. 68, 117–124 (2014).
- 42 . A slow-release system of bacterial cellulose gel and nanoparticles for hydrophobic active ingredients. Int. J. Pharm. 486(1–2), 217–225 (2015).
- 43 Bacterial cellulose/graphene oxide nanocomposite as a novel drug-delivery system. Curr. Appl. Phys. 17(2), 249–254 (2017).
- 44 . Development of bacterial cellulose based slow-release active films by incorporation of Scrophularia striata Boiss extract. Carbohyd. Polym. 156, 340–350 (2017). • Description of using cyclodextrins as carrier in BNC for poorly soluble substances.
- 45 . Antimicrobial porous hybrids consisting of bacterial nanocellulose and silver nanoparticles. Cellulose 20(2), 771–783 (2013).
- 46 . Bacterial cellulose-zinc oxide nanocomposites as a novel dressing system for burn wounds. Carbohyd. Polym. 164, 214–221 (2017).
- 47 . Freeze dried bacterial nanocellulose as potential drug-delivery system for peroral application of sensitive drugs. Presented at: CRS Local German Chapter Annual Meeting. Würzburg, Germany, 29–30 March 2012.
- 48 Nata de coco industry in Vietnam, Thailand, and Indonesia. In: Bacterial Nanocellulose – From Biotechnology to Bio-Economy. Gama M, Dourado F, Bielecki S (Eds). Elsevier, Amsterdam, The Netherlands, 231–236 (2016).
- 49 . Nata de coco industry in the Philippines. In: Bacterial Nanocellulose – From Biotechnology to Bio-Economy. Gama M, Dourado F, Bielecki S (Eds). Elsevier, Amsterdam, The Netherlands, 215–229 (2016).
- 50 . White biotechnology for cellulose manufacturing – the HoLiR concept. Biotechnol. Bioeng. 105(4), 740–747 (2010). •• First description of a (semi-)continuous upscale of BNC production.
- 51 . Production of bacterial cellulose membranes in a modified airlift bioreactor by Gluconacetobacter xylinus. J. Biosci. Bioeng. 120(4), 444–449 (2015).
- 52 . More than meets the eye in bacterial cellulose: biosynthesis, bioprocessing, and applications in advanced fiber composites. Macromol. Biosci. 14(1), 10–32 (2014).
- 53 . Bacterial cellulose films: influence of bacterial strain and drying route on film properties. Cellulose 21(6), 4455–4469 (2014).
- 54 . Bacterial cellulose and bacterial cellulose-vaccarin membranes for wound healing. Mater. Sci. Eng. C. Mater. Biol. Appl. 59, 303–309 (2016).
- 55 Bacterial nanocellulose with a shape-memory effect as potential drug-delivery system. RSC Adv. 4(100), 57173–57184 (2014).
- 56 . Controlled delivery of ampicillin and gentamycin from cellulose hydrogels and their antibacterial efficiency. J. Biomater. Tiss. Eng. 4(7), 543–549(547), (2014).