Nanotechnological Drug Release Systems In Oral Diseases

A Review



Dentistry, Drug Release Systems, Nanotechnology, Oral Cancer, Periodontal Disease


Nanotechnology is an interdisciplinary field which have been on the focus of most researches carried out in the field of health in recent years. Nanotechnological drug release systems developed with nanotechnology have gained ground in many fields of medicine and have brought about innumerous advantages. The small sizes and high surface areas of nano-scale particles provide chemically more reactive and superior electrical, magnetic, optical, biological or mechanical properties compared to their macroscopic or microscopic counterparts. Thanks to their superior physicochemical and biological properties, nanotechnological drugs are involved in the diagnosis, prevention and treatment of oral diseases such as dental caries, periodontal diseases, peri-implantitis, pulp and periapical lesions, denture stomatitis, hyposalivation, oral cancer and oral candidiasis. Nanotecnological drug delivery systems have taken an active role in the treatment of periodontal diseases and oral cancers, for they perform a long-term release in the mouth. This review study is aimed to explain the effects of nanotechnological drug delivery systems in the treatment of periodontal diseases and oral cancers, which will be examined under the title of oral diseases.


[1] Rudramurthy GR, Swamy MK. Potential applications of engineered nanoparticles in medicine and biology: an update. J Biol Inorg Chem (2018) 23(8):1185–1204.
[2] Mercadante V, Scarpa E, Matteis V de, Rizzello L, Poma A. Engineering Polymeric Nanosystems against Oral Diseases. Molecules (2021) 26(8).
[3] H RR, Dhamecha D, Jagwani S, Rao M, Jadhav K, Shaikh S, et al. Local drug delivery systems in the management of periodontitis: A scientific review. J Control Release (2019) 307:393–409.
[4] Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol (2015) 15(1):30–44.
[5] Petersen PE, Ogawa H. Strengthening the prevention of periodontal disease: the WHO approach. J Periodontol (2005) 76(12):2187–2193.
[6] Cafferata EA, Alvarez C, Diaz KT, Maureira M, Monasterio G, Gonzalez FE, et al. Multifunctional nanocarriers for the treatment of periodontitis: Immunomodulatory, antimicrobial, and regenerative strategies. Oral Dis (2019) 25(8):1866–1878.
[7] Noble JM, Scarmeas N, Papapanou PN. Poor oral health as a chronic, potentially modifiable dementia risk factor: review of the literature. Curr Neurol Neurosci Rep (2013) 13(10):384.
[8] Bui FQ, Almeida-da-Silva CLC, Huynh B, Trinh A, Liu J, Woodward J, et al. Association between periodontal pathogens and systemic disease. Biomed J (2019) 42(1):27–35.
[9] Chen X, Wu G, Feng Z, Dong Y, Zhou W, Li B, et al. Advanced biomaterials and their potential applications in the treatment of periodontal disease. Crit Rev Biotechnol (2016) 36(4):760–775.
[10] Abou Neel EA, Bozec L, Perez RA, Kim HW, Knowles JC. Nanotechnology in dentistry: prevention, diagnosis, and therapy. Int J Nanomedicine (2015) 10:6371–6394.
[11] Schwach-Abdellaoui K, Vivien-Castioni N, Gurny R. Local delivery of antimicrobial agents for the treatment of periodontal diseases. Eur J Pharm Biopharm (2000) 50(1):83–99.
[12] Pinon-Segundo E, Ganem-Quintanar A, Alonso-Perez V, Quintanar-Guerrero D. Preparation and characterization of triclosan nanoparticles for periodontal treatment. Int J Pharm (2005) 294(1-2):217–232.
[13] Hau H, Rohanizadeh R, Ghadiri M, Chrzanowski W. A mini-review on novel intraperiodontal pocket drug delivery materials for the treatment of periodontal diseases. Drug Deliv Transl Res (2014) 4(3):295–301.
[14] Pragati S, Ashok S, Kuldeep S. Recent advances in periodontal drug delivery systems. International Journal of Drug Delivery (2009) 1:1–14.
[15] Kornman KS. Controlled-Release Local Delivery Antimicrobials in Periodontics: Prospects for the Future. J Periodontol (1993) 64 Suppl 8S:782–791.
[16] Lee SJ, Heo DN, Lee D, Heo M, Rim H, Zhang LG, et al. One-Step Fabrication of AgNPs Embedded Hybrid Dual Nanofibrous Oral Wound Dressings. J Biomed Nanotechnol (2016) 12(11):2041–2050.
[17] He Y, Jin Y, Wang X, Yao S, Li Y, Wu Q, et al. An Antimicrobial Peptide-Loaded Gelatin/Chitosan Nanofibrous Membrane Fabricated by Sequential Layer-by-Layer Electrospinning and Electrospraying Techniques. Nanomaterials (Basel) (2018) 8(5).
[18] Mahmoud MY, Sapare S, Curry KC, Demuth DR, Steinbach-Rankins JM. Rapid Release Polymeric Fibers for Inhibition of Porphyromonas gingivalis Adherence to Streptococcus gordonii. Front Chem (2019) 7:926.
[19] Tokajuk G, Niemirowicz K, Deptula P, Piktel E, Ciesluk M, Wilczewska AZ, et al. Use of magnetic nanoparticles as a drug delivery system to improve chlorhexidine antimicrobial activity. Int J Nanomedicine (2017) 12:7833–7846.
[20] Regiel-Futyra A, Kus-Liskiewicz M, Sebastian V, Irusta S, Arruebo M, Stochel G, et al. Development of noncytotoxic chitosan-gold nanocomposites as efficient antibacterial materials. ACS Appl Mater Interfaces (2015) 7(2):1087–1099.
[21] Li C, Li Z, Wang Y, Liu H. Gold Nanoparticles Promote Proliferation of Human Periodontal Ligament Stem Cells and Have Limited Effects on Cells Differentiation. Journal of Nanomaterials (2016) 2016:1431836. doi:10.1155/2016/1431836.
[22] Yu Q, Li J, Zhang Y, Wang Y, Liu L, Li M. Inhibition of gold nanoparticles (AuNPs) on pathogenic biofilm formation and invasion to host cells. Sci Rep (2016) 6:26667.
[23] Madhumathi K, Sampath Kumar TS. Regenerative potential and anti-bacterial activity of tetracycline loaded apatitic nanocarriers for the treatment of periodontitis. Biomed Mater (2014) 9(3):35002.
[24] Kovtun A, Kozlova D, Ganesan K, Biewald C, Seipold N, Gaengler P, et al. Chlorhexidine-loaded calcium phosphate nanoparticles for dental maintenance treatment: combination of mineralising and antibacterial effects. RSC Advances (2012) 2(3):870–875. doi:10.1039/C1RA00955A.
[25] Kalia P, Jain A, Radha Krishnan R, Demuth DR, Steinbach-Rankins JM. Peptide-modified nanoparticles inhibit formation of Porphyromonas gingivalis biofilms with Streptococcus gordonii. Int J Nanomedicine (2017) 12:4553–4562.
[26] Backlund CJ, Worley BV, Sergesketter AR, Schoenfisch MH. Kinetic-dependent Killing of Oral Pathogens with Nitric Oxide. J Dent Res (2015) 94(8):1092–1098.
[27] Bao X, Zhao J, Sun J, Hu M, Yang X. Polydopamine Nanoparticles as Efficient Scavengers for Reactive Oxygen Species in Periodontal Disease. ACS Nano (2018) 12(9):8882–8892.
[28] Alvarez Echazu MI, Olivetti CE, Peralta I, Alonso MR, Anesini C, Perez CJ, et al. Development of pH-responsive biopolymer-silica composites loaded with Larrea divaricata Cav. extract with antioxidant activity. Colloids Surf B Biointerfaces (2018) 169:82–91.
[29] Pereira A, Brito GAC, Lima MLS, Silva Junior, A. A. D., Silva EDS, Rezende AA de, et al. Metformin Hydrochloride-Loaded PLGA Nanoparticle in Periodontal Disease Experimental Model Using Diabetic Rats. Int J Mol Sci (2018) 19(11).
[30] Zambrano LMG, Brandao DA, Rocha FRG, Marsiglio RP, Longo IB, Primo FL, et al. Local administration of curcumin-loaded nanoparticles effectively inhibits inflammation and bone resorption associated with experimental periodontal disease. Sci Rep (2018) 8(1):6652.
[31] Botelho MA, Martins JG, Ruela RS, Queiroz DB, Ruela WS. Nanotechnology in ligature-induced periodontitis: protective effect of a doxycycline gel with nanoparticules. J Appl Oral Sci (2010) 18(4):335–342.
[32] Lin JH, Feng F, Yu MC, Wang CH, Chang PC. Modulation of periodontitis progression using pH-responsive nanosphere encapsulating metronidazole or N-phenacylthialzolium bromide. J Periodontal Res (2018) 53(1):22–28.
[33] Mou J, Liu Z, Liu J, Lu J, Zhu W, Pei D. Hydrogel containing minocycline and zinc oxide-loaded serum albumin nanopartical for periodontitis application: preparation, characterization and evaluation. Drug Deliv (2019) 26(1):179–187.
[34] Osorio R, Alfonso-Rodriguez CA, Medina-Castillo AL, Alaminos M, Toledano M. Bioactive Polymeric Nanoparticles for Periodontal Therapy. PLoS One (2016) 11(11):e0166217.
[35] Wijetunge SS, Wen J, Yeh CK, Sun Y. Wheat germ agglutinin liposomes with surface grafted cyclodextrins as bioadhesive dual-drug delivery nanocarriers to treat oral cells. Colloids Surf B Biointerfaces (2020) 185:110572.
[36] Vidal-Romero G, Zambrano-Zaragoza ML, Martinez-Acevedo L, Leyva-Gomez G, Mendoza-Elvira SE, Quintanar-Guerrero D. Design and Evaluation of pH-Dependent Nanosystems Based on Cellulose Acetate Phthalate, Nanoparticles Loaded with Chlorhexidine for Periodontal Treatment. Pharmaceutics (2019) 11(11).
[37] Napimoga MH, Da Silva CA, Carregaro V, Farnesi-de-Assuncao TS, Duarte PM, Melo NF de, et al. Exogenous administration of 15d-PGJ2-loaded nanocapsules inhibits bone resorption in a mouse periodontitis model. J Immunol (2012) 189(2):1043–1052.
[38] Srivastava M, Neupane YR, Kumar P, Kohli K. Nanoemulgel (NEG) of Ketoprofen with eugenol as oil phase for the treatment of ligature-induced experimental periodontitis in Wistar rats. Drug Deliv (2016) 23(7):2228–2234.
[39] Khajuria DK, Zahra SF, Razdan R. Effect of locally administered novel biodegradable chitosan based risedronate/zinc-hydroxyapatite intra-pocket dental film on alveolar bone density in rat model of periodontitis. J Biomater Sci Polym Ed (2018) 29(1):74–91.
[40] Ni C, Zhou J, Kong N, Bian T, Zhang Y, Huang X, et al. Gold nanoparticles modulate the crosstalk between macrophages and periodontal ligament cells for periodontitis treatment. Biomaterials (2019) 206:115–132.
[41] WHO. I. Cancer Fact Sheets (2021).
[42] Mercadante V, Paderni C, Campisi G. Novel non-invasive adjunctive techniques for early oral cancer diagnosis and oral lesions examination. Curr Pharm Des (2012) 18(34):5442–5451.
[43] Jafari A, Najafi S, Moradi F, Kharazifard M, Khami M. Delay in the diagnosis and treatment of oral cancer. J Dent (Shiraz) (2013) 14(3):146–150.
[44] Mohan A, Narayanan S, Balasubramanian G, Sethuraman S, Krishnan UM. Dual drug loaded nanoliposomal chemotherapy: A promising strategy for treatment of head and neck squamous cell carcinoma. Eur J Pharm Biopharm (2016) 99:73–83.
[45] Baldea I, Florea A, Olteanu D, Clichici S, David L, Moldovan B, et al. Effects of silver and gold nanoparticles phytosynthesized with Cornus mas extract on oral dysplastic human cells. Nanomedicine (Lond) (2020) 15(1):55–75.
[46] Medina-Alarcon KP, Voltan AR, Fonseca-Santos B, Moro IJ, Oliveira Souza F de, Chorilli M, et al. Highlights in nanocarriers for the treatment against cervical cancer. Mater Sci Eng C Mater Biol Appl (2017) 80:748–759.
[47] Sundar S, Prajapati VK. Drug targeting to infectious diseases by nanoparticles surface functionalized with special biomolecules. Curr Med Chem (2012) 19(19):3196–3202.
[48] Calixto G, Bernegossi J, Fonseca-Santos B, Chorilli M. Nanotechnology-based drug delivery systems for treatment of oral cancer: a review. Int J Nanomedicine (2014) 9:3719–3735.
[49] El-Hamid ESA, Gamal-Eldeen AM, Sharaf Eldeen AM. Liposome-coated nano doxorubicin induces apoptosis on oral squamous cell carcinoma CAL-27 cells. Arch Oral Biol (2019) 103:47–54.
[50] Moradzadeh Khiavi M, Anvari E, Hamishehkar H, Abdal K. Assessment of the Blood Parameters, Cardiac and Liver Enzymes in Oral Squamous Cell Carcinoma Following Treated with Injectable Doxorubicin-Loaded Nano-Particles. Asian Pac J Cancer Prev (2019) 20(7):1973–1977.
[51] Wang Y, Wan G, Li Z, Shi S, Chen B, Li C, et al. PEGylated doxorubicin nanoparticles mediated by HN-1 peptide for targeted treatment of oral squamous cell carcinoma. Int J Pharm (2017) 525(1):21–31.
[52] Liu Z, Shi J, Zhu B, Xu Q. Development of a multifunctional gold nanoplatform for combined chemo-photothermal therapy against oral cancer. Nanomedicine (Lond) (2020) 15(7):661–676.
[53] Shtenberg Y, Goldfeder M, Prinz H, Shainsky J, Ghantous Y, Abu El-Naaj I, et al. Mucoadhesive alginate pastes with embedded liposomes for local oral drug delivery. Int J Biol Macromol (2018) 111:62–69.
[54] Xiong J, Feng J, Qiu L, Gao Z, Li P, Pang L, et al. SDF-1-loaded PLGA nanoparticles for the targeted photoacoustic imaging and photothermal therapy of metastatic lymph nodes in tongue squamous cell carcinoma. Int J Pharm (2019) 554:93–104.
[55] Endo K, Ueno T, Kondo S, Wakisaka N, Murono S, Ito M, et al. Tumor-targeted chemotherapy with the nanopolymer-based drug NC-6004 for oral squamous cell carcinoma. Cancer Sci (2013) 104(3):369–374.
[56] Wang D, Xu X, Zhang K, Sun B, Wang L, Meng L, et al. Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles-polymerpolyethylenimine to improve oral squamous carcinoma treatment. Int J Nanomedicine (2018) 13:187–198.
[57] Bharadwaj R, Sahu BP, Haloi J, Laloo D, Barooah P, Keppen C, et al. Combinatorial therapeutic approach for treatment of oral squamous cell carcinoma. Artif Cells Nanomed Biotechnol (2019) 47(1):572–585.
[58] Chang PY, Peng SF, Lee CY, Lu CC, Tsai SC, Shieh TM, et al. Curcumin-loaded nanoparticles induce apoptotic cell death through regulation of the function of MDR1 and reactive oxygen species in cisplatin-resistant CAR human oral cancer cells. Int J Oncol (2013) 43(4):1141–1150.
[59] Pornpitchanarong C, Rojanarata T, Opanasopit P, Ngawhirunpat T, Patrojanasophon P. Catechol-modified chitosan/hyaluronic acid nanoparticles as a new avenue for local delivery of doxorubicin to oral cancer cells. Colloids Surf B Biointerfaces (2020) 196:111279.
[60] Afrasiabi M, Seydi E, Rahimi S, Tahmasebi G, Jahanbani J, Pourahmad J. The selective toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) on oral squamous cell carcinoma (OSCC) by targeting their mitochondria. J Biochem Mol Toxicol (2021) 35(6):1–8.
[61] Lima JM de, Castellano LRC, Bonan PRF, Medeiros ES de, Hier M, Bijian K, et al. Chitosan/PCL nanoparticles can improve anti-neoplastic activity of 5-fluorouracil in head and neck cancer through autophagy activation. Int J Biochem Cell Biol (2021) 134:105964.
[62] Wang X, Jin J, Li W, Wang Q, Han Y, Liu H. Differential in vitro sensitivity of oral precancerous and squamous cell carcinoma cell lines to 5-aminolevulinic acid-mediated photodynamic therapy. Photodiagnosis Photodyn Ther (2020) 29:101554.
[63] Wang X, Li S, Liu H. Co-delivery of chitosan nanoparticles of 5-aminolevulinic acid and shGBAS for improving photodynamic therapy efficacy in oral squamous cell carcinomas. Photodiagnosis Photodyn Ther (2021) 34:102218.




How to Cite

Nanotechnological Drug Release Systems In Oral Diseases: A Review. (2022). International Journal of Innovative Research and Reviews, 6(1), 42-50.

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