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Fengxiang, G. Chitosan Nanostructures. Encyclopedia. Available online: (accessed on 09 December 2023).
Fengxiang G. Chitosan Nanostructures. Encyclopedia. Available at: Accessed December 09, 2023.
Fengxiang, Gao. "Chitosan Nanostructures" Encyclopedia, (accessed December 09, 2023).
Fengxiang, G.(2021, November 04). Chitosan Nanostructures. In Encyclopedia.
Fengxiang, Gao. "Chitosan Nanostructures." Encyclopedia. Web. 04 November, 2021.
Chitosan Nanostructures

Chitosan (CS) is a natural polymer with a positive charge, a deacetylated derivative of chitin. Chitosan nanostructures (nano-CS) have received increasing interest due to their potential applications and remarkable properties. 

nano-chitosan tissue engineering drug carry

1. Introduction

The oral cavity is a complex microenvironment that is vulnerable to various physical, chemical, and microbial injuries, resulting in oral diseases. These include soft tissue diseases, such as gingivitis, aphthous ulcers, and other mucosal diseases; hard tissue diseases, such as caries, fractures, and bone defects; and combined soft and hard tissue diseases, such as periodontitis and tumors. Therefore, in stomatology, it is necessary to find a medical material that features different characteristics under different treatment conditions. In recent years, many researchers have found that nano-chitosan offers application advantages against various oral diseases [1][2][3][4][5][6].
Chitosan (CS) is a cationic polymer composed of β-(1-4)-linked d-glucosamine and N-acetyl-d-glucosamine [7][8]. The cationic properties of CS enable it to combine with polyanions to form complexes; it also features gelation characteristics [9]. Furthermore, many of the characteristics of CS, such as its low water and acid solubility, good biodegradability, good biocompatibility, non-toxicity, antibacterial ability, anti-plaque effects, and anti-adhesion properties, allow the application of CS in many fields, especially in stomatology [7][9][10]. Intermolecular hydrogen bonding enables nano-CS to form stable nanogels, which feature a smaller size and higher specific surface area than CS [10][11][12][13]. Moreover, nanoscale confers certain characteristics upon nano-CS that are not present in CS. These characteristics include higher permeability, better biocompatibility, higher charge density, and greater support for the development of cells. These unique characteristics of nano-CS enable its abundant applications in stomatology (shown in Figure 1).
Figure 1. Common forms of nano-chitosan and their application in stomatology (Picture material cited from (accessed on 10 September 2021) and [4]).

2. Application of Nano-CS as Drug Carriers in Oral Soft Tissue Diseases

In different treatment methods for oral diseases (such as mucosal diseases, periodontitis, etc.), local drug administration with targeted- and sustained-release characteristics is preferable to systemic administration. Local administration can reduce the toxicity and side effects of drugs that are absorbed by other tissues or organs [4][14]. However, determining how locally administered drugs can be retained in the targeted tissue for a long time and released slowly in the presence of saliva and food-chewing remains challenging [4].
Chitosan is often used as a carrier for targeted drug delivery, to sustain drug effects at a subcellular scale, to achieve cellular targets with high accuracy, to achieve maximum therapeutic effect, and to decrease adverse effects [15][16][17]. In this approach, active drug substances are dissolved, entrapped, or encapsulated and absorbed or attached to the drug carriers [16][18]. Cationic CS can be electrostatically adsorbed with mucin carboxyl groups on the mucosal and enamel surface, in order to stay in the oral cavity for more than 6 h, and the film-forming ability of CS makes the drugs or biomolecules it is carrying release slowly [3][4][18][19]. When the pH of the oral environment is lower than 6.5 (the ionization constant of CS), CS can dissolve in water and release any drug or bioactive molecule it is carrying [20]. For instance, nano-CS has the ability to stably and continuously increase the release of NaF in an acidic environment with a pH of 5 to 7 [1][20]. Therefore, as a drug carrier, CS has considerable application prospects in acidic oral microenvironments. The small size of nanoscale increases the probability of biological membrane penetration by drugs carried by nano drug carriers, significantly increasing the bioavailability of the drugs and reducing their toxicity and side effects [17][21]. For example, compared to silver diamine fluoride alone, nano silver fluoride (NSF), which is composed of nanoparticles of silver and CS, has a lower effective dose against Streptococcus mutans and lower toxicity [22].
Nano-CS may have many effects in local oral administration, such as targeted adhesion to the surface of oral tissues, slow drug release, resistance to acidic oral environments, the improvement of drug bioavailability, and so on.
Nano-CS obtained by gamma irradiation, which is covered by bacterial cellulose, could significantly inhibit microbial strains in difficult-to-heal oral wounds [23]. This antimicrobial activity can inhibit bacterial invasion to protect the wound from secondary infection [23]. Nano-CS has a disc-like shape and an average diameter in the range of 40 to 60 nm. However, the release of nano-CS from BC is slow and continuous [23]. Tee [11] formed nano-CS loaded with recombinant human keratinocyte growth factor (nano-CS/rHuKGF) to increase the stability of rHuKGF and prevent rHuKGF proteolysis in saliva. Hydroxy-modified glucose CS (HGC) nanoparticles were synthesized by conjugating hydrophilic glycol CS with hydrophobic β-cholanic acid, and the synthesized nanoparticles showed good solubility in neutral solution, could self-assemble in neutral solution, and could encapsulate drugs for sustained release [24][25]. The core of the HGC nanoparticles was composed of hydrophobic β-cholanic acid covered by a hydrophilic cationic CS shell (shown in Figure 2). Drugs such as anionic trichloroacetic acid (TCA) and epidermal growth factor (EGF) can be loaded through ionic bonds (shown in Figure 3) [17][26]. The nano-controlled release system significantly reduced the danger of applying TCA locally [17]. Further, the nano-controlled release system upregulated the cell survival genes of the PI3K-AKT signaling pathway [26]. The system significantly increased the expression of gingival growth factors and soft tissue growth-related genes and significantly promoted soft tissue regeneration in animal experiments [17]. Therefore, HGC nanoparticles are an ideal nano-controlled release system for improving soft tissue regeneration. Doxycycline covered by nano-CS was utilized as an adjunct to basic periodontal therapy for moderate chronic periodontitis. Compared to traditional doxycycline and placebo-CS, gingival crevicular fluid levels of interleukin (IL)-6 and tumor necrosing factor-α significantly decreased, which was thought to have resulted from reduced inflammatory processes associated with tissue destruction in periodontal pockets. As a local delivery system, doxycycline covered by nano-CS is easy to apply and insert, which is suitable for the dimensions of the pocket, and it is easy to access the bottom of the pocket, reducing the pain of ingesting the medicine [27].
Figure 2. Preparation of HGC-based nano-controlled release system. CS was conjugated with hydrophobic cholanic acid. Hydrophobic cholanic acid is located inside the nanoparticles in water, and the hydrophilic cationic polymer amine group (NH2) of CS forms the structure of the nanoparticles. Cationic CS loads anions, TCA, and EGF through ionic bonds. Reprinted with permission from ref. [17]. Copyright 2021 Springer Nature.


  1. Nguyen, S.; Escudero, C.; Sediqi, N.; Smistad, G.; Hiorth, M. Fluoride loaded polymeric nanoparticles for dental delivery. Eur. J. Pharm. Sci. 2017, 104, 326–334.
  2. Osi, A.R.; Zhang, H.; Chen, J.; Zhou, Y.; Wang, R.; Fu, J.; Müller-Buschbaum, P.; Zhong, Q. Three-Dimensional-Printable Thermo/Photo-Cross-Linked Methacrylated Chitosan–Gelatin Hydrogel Composites for Tissue Engineering. ACS Appl. Mater. Interfaces 2021, 13, 22902–22913.
  3. Takeuchi, I.; Kamiki, Y.; Makino, K. Therapeutic efficacy of rebamipide-loaded PLGA nanoparticles coated with chitosan in a mouse model for oral mucositis induced by cancer chemotherapy. Colloids Surfaces B Biointerfaces 2018, 167, 468–473.
  4. Makvandi, P.; Josic, U.; Delfi, M.; Pinelli, F.; Jahed, V.; Kaya, E.; Ashrafizadeh, M.; Zarepour, A.; Rossi, F.; Zarrabi, A.; et al. Drug Delivery (Nano)Platforms for Oral and Dental Applications: Tissue Regeneration, Infection Control, and Cancer Management. Adv. Sci. 2021, 8, 2004014.
  5. Du, X.; Wu, L.; Yan, H.; Jiang, Z.; Li, S.; Li, W.; Bai, Y.; Wang, H.; Cheng, Z.; Kong, D.; et al. Microchannelled alkylated chitosan sponge to treat noncompressible hemorrhages and facilitate wound healing. Nat. Commun. 2021, 12, 4733.
  6. Arafa, M.G.; Mousa, H.A.; Afifi, N.N. Preparation of PLGA-chitosan based nanocarriers for enhancing antibacterial effect of ciprofloxacin in root canal infection. Drug Deliv. 2019, 27, 26–39.
  7. Sangeetha, K.; Alsharani, F.A.; Vinodhini, P.A.; Sudha, P.N.; Jayachandran, V.; Sukumaran, A. Antimicrobial efficacy of novel nanochitosan-based mat via electrospinning technique. Polym. Bull. 2018, 75, 5599–5618.
  8. Ikono, R.; Vibriani, A.; Wibowo, I.; Saputro, K.E.; Muliawan, W.; Bachtiar, B.M.; Mardliyati, E.; Bachtiar, E.W.; Rochman, N.T.; Kagami, H.; et al. Nanochitosan antimicrobial activity against Streptococcus mutans and Candida albicans dual-species biofilms. BMC Res. Notes 2019, 12, 1–7.
  9. Sadeghi, Z.; Iran University of Medical Science; Falahati, M.; Rostamkhani, F.A.; Bahador, A.; Alborzi, S.S.; Khozani, M.A.; Shahid Beheshti University of Medical Sciences; Ardestani, Z.S. The effect of acrylic resins containing nanochitosan particles on the formation of Candida species biofilms isolated from the mouths of Subjects. Curr. Med. Mycol. 2016, 2, 28–33.
  10. Aliasghari, A.; Khorasgani, M.R.; Vaezifar, S.; Rahimi, F.; Younesi, H.; Khoroushi, M. Evaluation of antibacterial efficiency of chitosan and chitosan nanoparticles on cariogenic streptococci: An in vitro study. Iran. J. Microbiol. 2016, 8, 93–100.
  11. Tee, Y.N.; Kumar, P.V.; Maki, M.A.; Elumalai, M.; Rahman, S.A.; Cheah, S.-C. Mucoadhesive Low Molecular Chitosan Complexes to Protect rHuKGF from Proteolysis: In-vitro Characterization and FHs 74 Int Cell Proliferation Studies. Curr. Pharm. Biotechnol. 2021, 22, 969–982.
  12. Rampino, A.; Borgogna, M.; Blasi, P.; Bellich, B.; Cesàro, A. Chitosan nanoparticles: Preparation, size evolution and stability. Int. J. Pharm. 2013, 455, 219–228.
  13. Akbari, H.R.; Mehrabadi, A.R.; Torabian, A. Determination of nanofiltration efficency in arsenic removal from drinking water. Iran. J. Environ. Health Sci. Eng. 2010, 7, 273–278.
  14. Rajeshwari, H.R.; Dhamecha, D.; Jagwani, S.; Rao, M.; Jadhav, K.; Shaikh, S.; Puzhankara, L.; Jalalpure, S. Local drug delivery systems in the management of periodontitis: A scientific review. J. Control. Release 2019, 307, 393–409.
  15. Fidya Effendi Chair, M.; Nurmawlidin Fauzia, M. The Influence of Pandalus Borealis Shell Nano Chitosan on Permanent Teeth Enamel Integrity against Caries. J. Int. Dent. Med. Res. 2019, 12, 487–491.
  16. Tarţǎu, L.; Lupuşoru, R.V.; Melnig, V. Experimental researches on the effects of nano-vesicles encapsulating dexketoprofen in a visceral pain model in mice. Ther. Pharmacol. Clin. Toxicol. 2010, 15, 202–206.
  17. Park, K.M.; Lee, H.J.; Koo, K.-T.; Ben Amara, H.; Leesungbok, R.; Noh, K.; Lee, S.C.; Lee, S.W. Oral Soft Tissue Regeneration Using Nano Controlled System Inducing Sequential Release of Trichloroacetic Acid and Epidermal Growth Factor. Tissue Eng. Regen. Med. 2020, 17, 91–103.
  18. Wassel, M.O.; Sherief, D. Ion release and enamel remineralizing potential of miswak, propolis and chitosan nano-particles based dental varnishes. Pediatr. Dent. J. 2019, 29, 1–10.
  19. Lee, H.-S.; Tsai, S.; Kuo, C.-C.; Bassani, A.W.; Pepe-Mooney, B.; Miksa, D.; Masters, J.; Sullivan, R.; Composto, R.J. Chitosan adsorption on hydroxyapatite and its role in preventing acid erosion. J. Colloid Interface Sci. 2012, 385, 235–243.
  20. Shen, P.; Bagheri, R.; Walker, G.; Yuan, Y.; Stanton, D.; Reynolds, C.; Reynolds, E. Effect of calcium phosphate addition to fluoride containing dental varnishes on enamel demineralization. Aust. Dent. J. 2016, 61, 357–365.
  21. Zeng, Z.W.; Wang, J.J.; Xiao, R.Z.; Xie, T.; Zhou, G.L.; Zhan, X.R.; Wang, S.L. Recent advances of chitosan nanoparticles as drug carriers. Int. J. Nanomed. 2011, 6, 765–774.
  22. Targino, A.G.R.; Flores, M.A.P.; Junior, V.E.D.S.; Bezerra, F.D.G.B.; Freire, H.D.L.; Galembeck, A.; Rosenblatt, A. An innovative approach to treating dental decay in children. A new anti-caries agent. J. Mater. Sci. Mater. Med. 2014, 25, 2041–2047.
  23. Zmejkoski, D.Z.; Marković, Z.M.; Budimir, M.D.; Zdravković, N.M.; Trišić, D.D.; Bugárová, N.; Danko, M.; Kozyrovska, N.O.; Špitalský, Z.; Kleinová, A.; et al. Photoactive and antioxidant nanochitosan dots/biocellulose hydrogels for wound healing treatment. Mater. Sci. Eng. C 2021, 122, 111925.
  24. Li, T.; Longobardi, L.; Granero-Molto, F.; Myers, T.J.; Yan, Y.; Spagnoli, A. Use of glycol chitosan modified by 5β-cholanic acid nanoparticles for the sustained release of proteins during murine embryonic limb skeletogenesis. J. Control. Release 2010, 144, 101–108.
  25. Kwon, S.; Park, J.H.; Chung, H.; Kwon, I.C.; Jeong, S.Y.; Kim, I.-S. Physicochemical Characteristics of Self-Assembled Nanoparticles Based on Glycol Chitosan Bearing 5β-Cholanic Acid. Langmuir 2003, 19, 10188–10193.
  26. Cho, J.Y.; Leesungbok, R.; Lee, S.W. Analysis of cell survival genes in human gingival fibroblasts after sequential release of trichloroacetic acid and epidermal growth factor using the nano-controlled release system. J. Dent. Rehabil. Appl. Sci. 2020, 36, 145–157.
  27. Madi, M.; Pavlic, V.; Samy, W.; Alagl, A. The anti-inflammatory effect of locally delivered nano-doxycycline gel in therapy of chronic periodontitis. Acta Odontol. Scand. 2017, 76, 71–76.
Subjects: Chemistry, Applied
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Update Date: 04 Nov 2021