Polysaccharide Nanocapsules for Drug Delivery Applications, Current Status and Future Perspectives

  • Marian FLOREA Valahia University of Targoviste, Romania
  • Rodica Mariana ION Valahia University of Targoviste, Romania; ICECHIM, Bucharest, Romania
Keywords: drug delivery, nanotechnology, nanocapsule, polysaccharide


In recent years pharmaceutical formulations using polymeric nanocapsules have been widely studied for developing novel drug delivery strategies. Nanocapsules provide a unique core-shell nanostructure, consisting of a liquid/solid core surrounded by a polymeric shell. Natural or modified polysaccharides are prime candidates for use as building blocks of the nanocapsule shells, due to their demonstrated safety, versatility and low cost and to the fact that they are widely used as excipients in classical drug formulations. The aim of this paper is to present the recent advances in drug delivery strategies using polysaccharidic nanocapsules and to discuss future opportunities and challenges in developing modern pharmaceutical formulations using such systems.

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[1]. Anselmo A. C., Mitragotri S., Nanoparticles in the clinic: An update, Bioeng. Transl. Med., vol. 4, no. 3, p. 1-16, doi: 10.1002/btm2.10143, 2019.
[2]. Posocco B. et al., Polysaccharides for the delivery of antitumor drugs, vol. 8, no. 5. 2015.
[3]. Deng S., Gigliobianco M. R., Censi R., Di Martino P., Polymeric nanocapsules as nanotechnological alternative for drug delivery system: Current status, challenges and opportunities, Nanomaterials, vol. 10, no. 5, doi: 10.3390/nano10050847, 2020.
[4]. Bussio J. I., Molina-Perea C., González-Aramundiz J. V., Hyaluronic acid nanocapsules as a platform for needle-free vaccination, Pharmaceutics, vol. 11, no. 5, p. 1-14, doi: 10.3390/pharmaceutics11050246, 2019.
[5]. Tekie F. S. M. et al., Nano polyelectrolyte complexes of carboxymethyl dextran and chitosan to improve chitosan-mediated delivery of miR-145, Carbohydr. Polym., vol. 159, p. 66-75, doi: 10.1016/j.carbpol.2016.11.067, 2017.
[6]. Chen C. K. et al., Synthesis of pH-responsive chitosan nanocapsules for the controlled delivery of doxorubicin, Langmuir, vol. 30, no. 14, p. 4111-4119, doi: 10.1021/la4040485, 2014.
[7]. Berger J., Reist M., Mayer J. M., Felt O., Peppas N. A., Gurny R., Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications, Eur. J. Pharm. Biopharm., vol. 57, no. 1, p. 19-34, doi: 10.1016/S0939-6411(03)00161-9, 2004.
[8]. Abozaid D., Ramadan A., Barakat H., Khalafallah N., Acyclovir lipid nanocapsules gel for oromucosal delivery: A preclinical evidence of efficacy in the chicken pouch membrane model, Eur. J. Pharm. Sci., vol. 121, no. 2017, p. 228-235, doi: 10.1016/j.ejps.2018.05.016, 2018.
[9]. Zhang H., Zhang F., Wu J., Physically crosslinked hydrogels from polysaccharides prepared by freeze-thaw technique, React. Funct. Polym., vol. 73, no. 7, p. 923-928, doi: 10.1016/j.reactfunctpolym.2012.12.014, 2013.
[10]. Shah N., Mewada R. K., Mehta T., Nano-Polysaccharides at Drug Delivery Systems, in International Conference on Multidisciplinary Research & Practice, vol. 1, no. 8, 2014.
[11]. Erdoğar N., Akkın S., Bilensoy E., Nanocapsules for Drug Delivery: An Updated Review of the Last Decade, Recent Pat. Drug Deliv. Formul., vol. 12, no. 4, p. 252-266, doi: 10.2174/1872211313666190123153711, 2019.
[12]. Marto J. M., Gouveia L. F., Gonçalves L. M. D., Ribeiro H. M., Almeida A. J., Design of minocycline- containing starch nanocapsules for topical delivery, J. Microencapsul., vol. 35, no. 4, p. 344-356, doi: 10.1080/02652048.2018.1487472, 2018.
[13]. Marto J. et al., A Quality by design (QbD) approach on starch-based nanocapsules: A promising platform for topical drug delivery, Colloids Surfaces B Biointerfaces, vol. 143, p. 177-185, doi: 10.1016/j.colsurfb.2016.03.039, 2016.
[14]. Paleos C. M., Sideratou Z., Tsiourvas D., Drug Delivery Systems Based on Hydroxyethyl Starch, Bioconjug. Chem., vol. 28, no. 6, p. 1611-1624, doi: 10.1021/acs.bioconjchem.7b00186, 2017.
[15]. Zhang Y., Chi C., Huang X., Zou Q., Li X., Chen L., Starch-based nanocapsules fabricated through layer-by-layer assembly for oral delivery of protein to lower gastrointestinal tract, Carbohydr. Polym., vol. 171, p. 242-251, doi: 10.1016/j.carbpol.2017.04.090, 2017.
[16]. Hasani S., Ojagh S. M., Ghorbani M., Nanoencapsulation of lemon essential oil in Chitosan-Hicap system. Part 1: Study on its physical and structural characteristics, Int. J. Biol. Macromol., vol. 115, p. 143-151, doi: 10.1016/j.ijbiomac.2018.04.038, 2018.
[17]. Li J. et al., Chitosan-based nanomaterials for drug delivery, Molecules, vol. 23, no. 10, p. 1-26, doi: 10.3390/molecules23102661, 2018.
[18]. Hussain R., Maji T. K., Maji T. K., Determination of degree of deacetylation of chitosan and their effect on the release behavior of essential oil from chitosan and chitosan-gelatin complex microcapsules, Rev. Téc. Ing. Univ. Zulia, vol. 37, p. 69-77, [Online]. Available: http://tjfeonline.com/admin/archive/719.09.20141411142742.pdf, 2014.
[19]. Miao T., Wang J., Zeng Y., Liu G., Chen X., Polysaccharide-Based Controlled Release Systems for Therapeutics Delivery and Tissue Engineering: From Bench to Bedside, Adv. Sci., vol. 5, no. 4, doi: 10.1002/advs.201700513, 2018.
[20]. Bussio J. I., Molina-Perea C., González-Aramundiz J. V., Lower-sized chitosan nanocapsules for transcutaneous antigen delivery, Nanomaterials, vol. 8, no. 9, p. 1-14, doi: 10.3390/nano8090659, 2018.
[21]. Bruinsmann F. A. et al., Chitosan-coated nanoparticles: Effect of chitosan molecular weight on nasal transmucosal delivery, Pharmaceutics, vol. 11, no. 2, p. 1-19, doi: 10.3390/pharmaceutics11020086, 2019.
[22]. Mohammed M. A., Syeda J. T. M., Wasan K. M., Wasan E. K., An overview of chitosan nanoparticles and its application in non-parenteral drug delivery, Pharmaceutics, vol. 9, no. 4, doi: 10.3390/pharmaceutics9040053, 2017.
[23]. Jing Z. W. et al., Chitosan cross-linked with poly(ethylene glycol)dialdehyde via reductive amination as effective controlled release carriers for oral protein drug delivery, Bioorganic Med. Chem. Lett., vol. 27, no. 4, p. 1003-1006, doi: 10.1016/j.bmcl.2016.12.072, 2017.
[24]. Ho T. H., Le T. N. T., Nguyen T. A., Dang M. C., Poly(ethylene glycol) grafted chitosan as new copolymer material for oral delivery of insulin, Adv. Nat. Sci. Nanosci. Nanotechnol., vol. 6, no. 3, p. 35004, doi: 10.1088/2043-6262/6/3/035004, 2015.
[25]. Belbekhouche S. et al., Chitosan based self-assembled nanocapsules as antibacterial agent, Colloids Surfaces B Biointerfaces, vol. 181, no. January, p. 158-165, doi: 10.1016/j.colsurfb.2019.05.028, 2019.
[26]. Kulkarni A. D., Patel H. M., Surana S. J., Vanjari Y. H., Belgamwar V. S., Pardeshi C. V., N,N,N-Trimethyl chitosan: An advanced polymer with myriad of opportunities in nanomedicine, Carbohydr. Polym., vol. 157, p. 875-902, doi: 10.1016/j.carbpol.2016.10.041, 2017.
[27]. Khan M. M. et al., Lipid-chitosan hybrid nanoparticles for controlled delivery of cisplatin, Drug Deliv., vol. 26, no. 1, p. 765-772, doi: 10.1080/10717544.2019.1642420, 2019.
[28]. Wang H., Pectin-Chitosan Polyelectrolyte Complex Nanoparticles for Encapsulation and Controlled Release of Nisin, Am. J. Polym. Sci. Technol., vol. 3, no. 5, p. 82, doi: 10.11648/j.ajpst.20170305.11, 2017.
[29]. Giri T. K., Ghosh B., Eds., Polysaccharide-based Nano-Biocarrier in Drug Delivery. Taylor & Francis, 2019.
[30]. Gopinath V., Saravanan S., Al-Maleki A. R., Ramesh M., Vadivelu J., A review of natural polysaccharides for drug delivery applications: Special focus on cellulose, starch and glycogen, Biomed. Pharmacother., vol. 107, no. April, p. 96-108, doi: 10.1016/j.biopha.2018.07.136, 2018.
[31]. Qing W., Wang Y., Wang Y., Zhao D., Liu X., Zhu J., The modified nanocrystalline cellulose for hydrophobic drug delivery, Appl. Surf. Sci., vol. 366, p. 404-409, doi: 10.1016/j.apsusc.2016.01.133, 2016.
[32]. Dai L., Si C. L., Cellulose-graft-poly(methyl methacrylate) nanoparticles with high biocompatibility for hydrophobic anticancer drug delivery, Mater. Lett., vol. 207, p. 213-216, doi: 10.1016/j.matlet.2017.07.090, 2017.
[33]. Liakos I. L. et al., Cellulose acetate - essential oil nanocapsules with antimicrobial activity for biomedical applications, Colloids Surfaces B Biointerfaces, vol. 172, p. 471-479, doi: 10.1016/j.colsurfb.2018.08.069, 2018.
[34]. Rao Z. et al., Carboxymethyl cellulose modified graphene oxide as pH-sensitive drug delivery system, Int. J. Biol. Macromol., vol. 107, no. Part A, p. 1184-1192, doi: 10.1016/j.ijbiomac.2017.09.096, 2018.
[35]. Roy J. C., Ferri A., Giraud S., Jinping G., Salaün F., Chitosan–carboxymethylcellulose-based polyelectrolyte complexation and microcapsule shell formulation, Int. J. Mol. Sci., vol. 19, no. 9, doi: 10.3390/ijms19092521, 2018.
[36]. Bekaroğlu M. G., İşçi Y., İşçi S., Colloidal properties and in vitro evaluation of Hydroxy ethyl cellulose coated iron oxide particles for targeted drug delivery, Mater. Sci. Eng. C, vol. 78, p. 847-853, doi: 10.1016/j.msec.2017.04.030, 2017.
[37]. Jacob J., Haponiuk J. T., Thomas S., Gopi S., Biopolymer based nanomaterials in drug delivery systems: A review, Mater. Today Chem., vol. 9, p. 43-55, doi: 10.1016/j.mtchem.2018.05.002, 2018.
[38]. Severino P., da Silva C. F., Andrade L. N., de Lima Oliveira D., Campos J., Souto E. B., Alginate Nanoparticles for Drug Delivery and Targeting, Curr. Pharm. Des., vol. 25, no. 11, p. 1312-1334, doi: 10.2174/1381612825666190425163424, 2019.
[39]. Aderibigbe B. A., Buyana B., Alginate in wound dressings, Pharmaceutics, vol. 10, no. 2, doi: 10.3390/pharmaceutics10020042, 2018.
[40]. Cheaburu-Yilmaz C. N., Lupuşoru C. E., Vasile C., New alginate/PNIPAAm matrices for drug delivery, Polymers (Basel)., vol. 11, no. 2, doi: 10.3390/POLYM11020366, 2019.
[41]. Wong T. W., Alginate graft copolymers and alginate-coexcipient physical mixture in oral drug delivery, J. Pharm. Pharmacol., vol. 63, no. 12, p. 1497-1512, doi: 10.1111/j.2042-7158.2011.01347.x, 2011.
[42]. Unagolla J. M., Jayasuriya A. C., Drug transport mechanisms and in vitro release kinetics of vancomycin encapsulated chitosan-alginate polyelectrolyte microparticles as a controlled drug delivery system, Eur. J. Pharm. Sci., vol. 114, p. 199-209, doi: 10.1016/j.ejps.2017.12.012, 2018.
[43]. Ye S., Wang C., Liu X., Tong Z., Multilayer nanocapsules of polysaccharide chitosan and alginate through layer-by-layer assembly directly on PS nanoparticles for release, J. Biomater. Sci. Polym. Ed., vol. 16, no. 7, p. 909-923, doi: 10.1163/1568562054255691, 2005.
[44]. Cuomo F., et al., Vesicle-templated layer-by-layer assembly for the production of nanocapsules, Langmuir, vol. 26, no. 13, p. 10555-10560, doi: 10.1021/la100584b, 2010.
[45]. Belbekhouche S. et al., Cationic poly(cyclodextrin)/alginate nanocapsules: From design to application as efficient delivery vehicle of 4-hydroxy tamoxifen to podocyte in vitro, Colloids Surfaces B Biointerfaces, vol. 179, no. January, p. 128-135, doi: 10.1016/j.colsurfb.2019.03.060, 2019.
[46]. Nurunnabi M., et al., Polysaccharide based nano/microformulation: An effective and versatile oral drug delivery system, Elsevier Inc., 2017.
[47]. Collins M. N., Birkinshaw C., Hyaluronic acid based scaffolds for tissue engineering - A review, Carbohydr. Polym., vol. 92, no. 2, p. 1262-1279, doi: 10.1016/j.carbpol.2012.10.028, 2013.
[48]. Noh I., Kim N., Tran H. N., Lee J., Lee C., 3D printable hyaluronic acid-based hydrogel for its potential application as a bioink in tissue engineering, Biomater. Res., vol. 23, no. 1, p. 1-9, doi: 10.1186/s40824-018-0152-8, 2019.
[49]. Cadete A. et al., Self-assembled hyaluronan nanocapsules for the intracellular delivery of anticancer drugs, Sci. Rep., vol. 9, no. 1, p. 1-11, doi: 10.1038/s41598-019-47995-8, 2019.
[50]. Rochín-Wong S. et al., Drug release properties of diflunisal from layer-by- layer self-assembled k-carrageenan/chitosan nanocapsules: Effect of deposited layers, Polymers (Basel)., vol. 10, no. 7, p. 1-16, doi: 10.3390/polym10070760, 2018.
[51]. Steinmacher F. R., Baier G., Musyanovych A., Landfester K., Araújo P. H. H., Sayer C., Design of cross-linked starch nanocapsules for enzyme-triggered release of hydrophilic compounds, Processes, vol. 5, no. 2, doi: 10.3390/pr5020025, 2017.
[52]. Dubey V., Mohan P., Dangi J. S., Kesavan K., Brinzolamide loaded chitosan-pectin mucoadhesive nanocapsules for management of glaucoma: Formulation, characterization and pharmacodynamic study, Int. J. Biol. Macromol., vol. 152, p. 1224-1232, doi: 10.1016/j.ijbiomac.2019.10.219, 2020.
[53]. Wajs E., Nielsen T. T., Larsen K. L., Fragoso A., Preparation of stimuli-responsive nano-sized capsules based on cyclodextrin polymers with redox or light switching properties, Nano Res., vol. 9, no. 7, p. 2070-2078, doi: 10.1007/s12274-016-1097-7, 2016.
[54]. Fessi H., Puisieux F., Devissaguet J. P., Ammoury N., Benita S., Nanocapsule formation by interfacial polymer deposition following solvent displacement, Int. J. Pharm., vol. 55, no. 1, p. 1-4, doi: 10.1016/0378-5173(89)90281-0, 1989.
[55]. Mora-Huertas C. E., Fessi H., Elaissari A., Influence of process and formulation parameters on the formation of submicron particles by solvent displacement and emulsification-diffusion methods: Critical comparison, Adv. Colloid Interface Sci., vol. 163, no. 2, p. 90-122, doi: 10.1016/j.cis.2011.02.005, 2011.
[56]. Quintanar-Guerrero D., Fessi H., Allémann E., Doelker E., Influence of stabilizing agents and preparative variables on the formation of poly(D,L-lactic acid) nanoparticles by an emulsification-diffusion technique,” Int. J. Pharm., vol. 143, no. 2, p. 133-141, doi: 10.1016/S0378-5173(96)04697-2, 1996.
[57]. Sombra F. M. et al., Development of amphotericin B-loaded propionate Sterculia striata polysaccharide nanocarrier, Int. J. Biol. Macromol., vol. 146, p. 1133-1141, doi: 10.1016/j.ijbiomac.2019.10.053, 2020.
[58]. Moise M. et al., Double crosslinked chitosan and gelatin submicronic capsules entrapping aminoacid derivatives with potential antitumoral activity, J. Mater. Sci., vol. 47, no. 23, p. 8223-8233, doi: 10.1007/s10853-012-6719-1, 2012.
[59]. Liu Y., Loh X. J., Polymer Capsules. Pan Stanford Publishing, 2019.
[60]. Pinheiro A. C. et al., Chitosan/fucoidan multilayer nanocapsules as a vehicle for controlled release of bioactive compounds, Carbohydr. Polym., vol. 115, p. 1-9, doi: 10.1016/j.carbpol.2014.07.016, 2015.
[61]. Szafraniec J., et al., Chitosan-based nanocapsules of coreshell architecture, Polimery/Polymers, vol. 62, no. 7-8, p. 713-719, doi: 10.14314/polimery.2017.713, 2017.
[62]. Elbaz N. M., et al., Controlled synthesis of calcium carbonate nanoparticles and stimuli-responsive multi-layered nanocapsules for oral drug delivery, Int. J. Pharm., vol. 574, p. 118866, doi: 10.1016/j.ijpharm.2019.118866, 2020.
[63]. Kamburova K., Mitarova K., Radeva T., Polysaccharidebased nanocapsules for controlled release of indomethacin, Colloids Surfaces A Physicochem. Eng. Asp., vol. 519, p. 199-204, doi: 10.1016/j.colsurfa.2016.05.040, 2017.
[64]. Crecente-Campo J. et al., Bilayer polymeric nanocapsules: A formulation approach for a thermostable and adjuvanted E. coli antigen vaccine, J. Control. Release, vol. 286, p. 20-32, doi: 10.1016/j.jconrel.2018.07.018, 2018.
[65]. Rivera M. C., Pinheiro A. C., Bourbon A. I., Cerqueira M. A., Vicente A. A., Hollow chitosan/alginate nanocapsules for bioactive compound delivery, Int. J. Biol. Macromol., vol. 79, p. 95-102, doi: 10.1016/j.ijbiomac.2015.03.003, 2015.
[66]. Wang W. et al., pH-responsive Capsaicin@chitosan nanocapsules for antibiofouling in marine applications, Polymer (Guildf)., vol. 158, no. August, p. 223-230, doi: 10.1016/j.polymer.2018.10.067, 2018.
[67]. Lee J. S. et al., A novel chitosan nanocapsule for enhanced skin penetration of cyclosporin A and effective hair growth in vivo, Nano Res., vol. 12, no. 1, p. 29-31, doi: 10.1007/s12274-019-2546-x, 2019.
[68]. Ji F. et al., Engineering pectin-based hollow nanocapsules for delivery of anticancer drug, Carbohydr. Polym., vol. 177, p. 86-96, doi: 10.1016/j.carbpol.2017.08.107, 2017.
[69]. Milosavljevic V. et al., Encapsulation of Doxorubicin in Furcellaran/Chitosan Nanocapsules by Layer-by-Layer Technique for Selectively Controlled Drug Delivery, Biomacromolecules, doi: 10.1021/acs.biomac.9b01175, 2019.
[70]. Son S et al., Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination, Nano Lett., vol. 20, no. 3, p. 1499-1509, doi: 10.1021/acs.nanolett.9b03483, 2020.
[71]. Yan X. et al., Programmable Hierarchical Construction of Mixed/Multilayered Polysaccharide Nanocapsules through Simultaneous/Sequential Nanoprecipitation Steps, Biomacromolecules, vol. 20, no. 10, p. 3915-3923, doi: 10.1021/acs.biomac.9b00990, 2019.
[72]. Matoso Sombra F. et al., Nanocapsules of Sterculia striata acetylated polysaccharide as a potential monomeric amphotericin B delivery matrix, Int. J. Biol. Macromol., vol. 130, p. 655-663, doi: 10.1016/j.ijbiomac.2019.02.076, 2019.
[73]. Shamekhi F., et al., Development of chitosan coated calcium-alginate nanocapsules for oral delivery of liraglutide to diabetic patients, Int. J. Biol. Macromol., vol. 120, p. 460-467, doi: 10.1016/j.ijbiomac.2018.08.078, 2018.
[74]. Ghadi R., Dand N., BCS class IV drugs: Highly notorious candidates for formulation development, J. Control. Release, vol. 248, p. 71-95, doi: 10.1016/j.jconrel.2017.01.014, 2017.
How to Cite
FLOREA M, ION RM. Polysaccharide Nanocapsules for Drug Delivery Applications, Current Status and Future Perspectives. The Annals of “Dunarea de Jos” University of Galati. Fascicle IX, Metallurgy and Materials Science [Internet]. 15Mar.2021 [cited 24Jul.2021];44(1):46-3. Available from: https://www.gup.ugal.ro/ugaljournals/index.php/mms/article/view/4322