Review| Volume 43, ISSUE 12, e377-e402, December 2021

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Applications of Novel and Nanostructured Drug Delivery Systems for the Treatment of Oral Cavity Diseases


      • Novel DDSs provide efficient controlled drug delivery for oral diseases.
      • Applications of nanofibers, nanoparticulates, hydrogels, and films are summarized.
      • New designs and in vivo efficacy of novel DDSs for oral diseases were described.



      Novel drug delivery systems (DDSs) hold great promise for the treatment of oral cavity diseases. The main objective of this article was to provide a detailed overview regarding recent advances in the use of novel and nanostructured DDSs in alleviating and treating unpleasant conditions of the oral cavity. Strategies to maximize the benefits of these systems in the treatment of oral conditions and future directions to overcome these issues are also discussed.


      Publications from the last 10 years investigating novel and nanostructured DDSs for pathologic oral conditions were browsed in a systematic search using the PubMed/MEDLINE, Web of Science, and Scopus databases. Research on applications of novel DDSs for periodontitis, oral carcinomas, oral candidiasis, xerostomia, lichen planus, aphthous stomatitis, and oral mucositis is summarized. A narrative exploratory review of the most recent literature was undertaken.


      Conventional systemic administration of therapeutic agents could exhibit high clearance of drugs from the bloodstream and low accumulation at the target site. In contrast, conventional topical systems face problems such as short residence time in the affected region and low patient compliance. Novel and nanostructured DDSs are among the most effective and commonly used methods for overcoming the problems of conventional DDSs. The main advantages of these systems are that they possess the ability to protect active agents from systemic and local clearance, enhance bioavailability and cellular uptake, and provide immediate or modified release of therapeutic agents after administration. In the design of local drug delivery devices such as nanofiber mats, films, and patches, components and excipients can significantly affect factors such as drug release rate, residence time in the oral cavity, and taste in the mouth. Choosing appropriate additives is therefore essential.


      Local drug delivery devices such as nanofiber mats, nanoparticles, liposomes, hydrogels, films, and patches for oral conditions can significantly affect drug efficacy and safety. However, more precise clinical studies should be designed and conducted to confirm promising in vitro and in vivo results. In recent years, novel and nanostructured DDSs increasingly attracted the attention of researchers as a means of treatment and alleviation of oral diseases and unpleasant conditions. However, more clinical studies should be performed to confirm promising in vitro and in vivo results. To transform a successful laboratory model into a marketable product, the long-term stability of prepared formulations is essential. Also, proper scale-up methods with optimum preparation costs should be addressed.

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        • Lee J
        • Watt R
        • Williams D
        • Giannobile W.
        A new definition for oral health: implications for clinical practice, policy, and research.
        SAGE Publications, Sage, CA and Los Angeles, CA2017
        • Sischo L
        • Broder H.
        Oral health-related quality of life: what, why, how, and future implications.
        Journal of dental research. 2011; 90: 1264-1270
        • Al-Harthi L
        • Cullinan M
        • Leichter J
        • Thomson W.
        The impact of periodontitis on oral health-related quality of life: a review of the evidence from observational studies.
        Australian dental journal. 2013; 58: 274-277
        • Kassebaum N
        • Smith A
        • Bernabé E
        • et al.
        Global, regional, and national prevalence, incidence, and disability-adjusted life years for oral conditions for 195 countries, 1990–2015: a systematic analysis for the global burden of diseases, injuries, and risk factors.
        Journal of dental research. 2017; 96: 380-387
        • Listl S
        • Galloway J
        • Mossey P
        • Marcenes W.
        Global economic impact of dental diseases.
        Journal of dental research. 2015; 94: 1355-1361
        • Griffin SO
        • Jones JA
        • Brunson D
        • Griffin PM
        • Bailey WD.
        Burden of oral disease among older adults and implications for public health priorities.
        American journal of public health. 2012; 102: 411-418
        • Warnakulasuriya S
        • Dietrich T
        • Bornstein MM
        • et al.
        Oral health risks of tobacco use and effects of cessation.
        International dental journal. 2010; 60: 7-30
        • Lalla RV
        • Saunders DP
        • Peterson DE.
        Chemotherapy or radiation-induced oral mucositis.
        Dental clinics. 2014; 58: 341-349
        • Markopoulos AK.
        Current aspects on oral squamous cell carcinoma.
        The open dentistry journal. 2012; 6: 126
        • Shojaei AH.
        Buccal mucosa as a route for systemic drug delivery: a review.
        Journal of pharmacy & pharmaceutical sciences. 1998; 1: 15-30
        • Hearnden V
        • Sankar V
        • Hull K
        • et al.
        New developments and opportunities in oral mucosal drug delivery for local and systemic disease.
        Advanced drug delivery reviews. 2012; 64: 16-28
        • Calixto G
        • Bernegossi J
        • Fonseca-Santos B
        • Chorilli M.
        Nanotechnology-based drug delivery systems for treatment of oral cancer: a review.
        International journal of nanomedicine. 2014; 9: 3719
        • Babadi D
        • Dadashzadeh S
        • Osouli M
        • Daryabari MS
        • Haeri A.
        Nanoformulation strategies for improving intestinal permeability of drugs: a more precise look at permeability assessment methods and pharmacokinetic properties changes.
        Journal of controlled release. 2020; 321: 669-709
        • Zhang H
        • Zhang J
        • Streisand JB.
        Oral mucosal drug delivery.
        Clinical pharmacokinetics. 2002; 41: 661-680
        • Yamahara H
        • Lee VH.
        Drug metabolism in the oral cavity.
        Advanced drug delivery reviews. 1993; 12: 25-39
        • Raza K
        • Kumar M
        • Kumar P
        • et al.
        Topical delivery of aceclofenac: challenges and promises of novel drug delivery systems.
        BioMed research international. 2014; (2014)
        • Sankar V
        • Hearnden V
        • Hull K
        • et al.
        Local drug delivery for oral mucosal diseases: challenges and opportunities.
        Oral diseases. 2011; 17: 73-84
        • Rosenblum D
        • Joshi N
        • Tao W
        • Karp JM
        • Peer D.
        Progress and challenges towards targeted delivery of cancer therapeutics.
        Nature communications. 2018; 9: 1-12
        • Ignatious F
        • Sun L
        • Lee C-P
        • Baldoni J.
        Electrospun nanofibers in oral drug delivery.
        Pharmaceutical research. 2010; 27: 576-588
        • Deepak A
        • Goyal AK
        • Rath G.
        Development and characterization of novel medicated nanofiber for the treatment of periodontitis.
        AAPS PharmSciTech. 2018; 19: 3687-3697
        • Villarreal-Gómez LJ
        • Cornejo-Bravo JM
        • Vera-Graziano R
        • Grande D.
        Electrospinning as a powerful technique for biomedical applications: a critically selected survey.
        Journal of biomaterials science, polymer edition. 2016; 27: 157-176
        • Samprasit W
        • Rojanarata T
        • Akkaramongkolporn P
        • Ngawhirunpat T
        • Kaomongkolgit R
        • Opanasopit P.
        Fabrication and in vitro/in vivo performance of mucoadhesive electrospun nanofiber mats containing α-mangostin.
        AAPS PharmSciTech. 2015; 16: 1140-1152
        • Alavi S
        • Haeri A
        • Dadashzadeh S.
        Utilization of chitosan-caged liposomes to push the boundaries of therapeutic delivery.
        Carbohydrate polymers. 2017; 157: 991-1012
        • Morales JO
        • McConville JT.
        Manufacture and characterization of mucoadhesive buccal films.
        European journal of pharmaceutics and biopharmaceutics. 2011; 77: 187-199
        • de Freitas L
        • Calixto G
        • Chorilli M
        • et al.
        Polymeric nanoparticle-based photodynamic therapy for chronic periodontitis in vivo.
        International journal of molecular sciences. 2016; 17: 769
        • Chaves P
        • Oliveira J
        • Haas A
        • Beck RC.
        Applications of polymeric nanoparticles in oral diseases: a review of recent findings.
        Current pharmaceutical design. 2018; 24: 1377-1394
        • Bayat F
        • Hosseinpour-Moghadam R
        • Mehryab F
        • et al.
        Potential application of liposomal nanodevices for non-cancer diseases: an update on design, characterization and biopharmaceutical evaluation.
        Advances in colloid and interface science. 2020; 277: 102121
        • Costalonga M
        • Herzberg MC.
        The oral microbiome and the immunobiology of periodontal disease and caries.
        Immunology letters. 2014; 162: 22-38
        • Buhlin K
        • Mäntylä P
        • Paju S
        • et al.
        Periodontitis is associated with angiographically verified coronary artery disease.
        Journal of clinical periodontology. 2011; 38: 1007-1014
        • Dhotre S
        • Jahagirdar V
        • Suryawanshi N
        • Davane M
        • Patil R
        • Nagoba B.
        Assessment of periodontitis and its role in viridans streptococcal bacteremia and infective endocarditis.
        Indian heart journal. 2018; 70: 225-232
        • Gomes-Filho IS
        • Leitão de Oliveira TF
        • Seixas da Cruz S
        • et al.
        Influence of periodontitis in the development of nosocomial pneumonia: a case control study.
        Journal of periodontology. 2014; 85: e82-e90
        • Whitmore SE
        • Lamont RJ.
        Oral bacteria and cancer.
        PLoS pathogens. 2014; 10: e1003933
        • Feres M
        • Soares GMS
        • Mendes JAV
        • et al.
        Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial.
        Journal of clinical periodontology. 2012; 39: 1149-1158
        • Hajishengallis G.
        Periodontitis: from microbial immune subversion to systemic inflammation.
        Nature reviews immunology. 2015; 15: 30
        • Graves D
        • Li J
        • Cochran D.
        Inflammation and uncoupling as mechanisms of periodontal bone loss.
        Journal of dental research. 2011; 90: 143-153
        • Zupančič Š
        • Preem L
        • Kristl J
        • et al.
        Impact of PCL nanofiber mat structural properties on hydrophilic drug release and antibacterial activity on periodontal pathogens.
        European journal of pharmaceutical sciences. 2018; 122: 347-358
        • Scapoli L
        • Girardi A
        • Palmieri A
        • et al.
        Quantitative analysis of periodontal pathogens in periodontitis and gingivitis.
        Journal of biological regulators & homeostatic agents. 2015; 29: 101-110
        • Genco RJ
        • Borgnakke WS.
        Risk factors for periodontal disease.
        Periodontology 2000. 2013; 62: 59-94
        • Ding G
        • Liu Y
        • Wang W
        • et al.
        Allogeneic periodontal ligament stem cell therapy for periodontitis in swine.
        Stem cells. 2010; 28: 1829-1838
        • Samprasit W
        • Kaomongkolgit R
        • Sukma M
        • Rojanarata T
        • Ngawhirunpat T
        • Opanasopit P.
        Mucoadhesive electrospun chitosan-based nanofibre mats for dental caries prevention.
        Carbohydrate polymers. 2015; 117: 933-940
        • Lamont T
        • Worthington HV
        • Clarkson JE
        • Beirne PV.
        Routine scale and polish for periodontal health in adults.
        The Cochrane database of systematic reviews. 2018; 12: CD004625
        • Khan G
        • Yadav SK
        • Patel RR
        • Kumar N
        • Bansal M
        • Mishra B.
        Tinidazole functionalized homogeneous electrospun chitosan/poly (ε-caprolactone) hybrid nanofiber membrane: development, optimization and its clinical implications.
        International journal of biological macromolecules. 2017; 103: 1311-1326
        • Chaturvedi T
        • Srivastava R
        • Srivastava A
        • Gupta V
        • Verma PK.
        Doxycycline poly e-caprolactone nanofibers in patients with chronic periodontitis—a clinical evaluation.
        Journal of clinical and diagnostic research. 2013; 7: 2339
        • 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 delivery. 2019; 26: 179-187
        • Yao W
        • Xu P
        • Zhao J
        • et al.
        RGD functionalized polymeric nanoparticles targeting periodontitis epithelial cells for the enhanced treatment of periodontitis in dogs.
        Journal of colloid and interface science. 2015; 458: 14-21
        • Pramod K
        • Aji Alex M
        • Singh M
        • Dang S
        • Ansari SH
        • Ali J
        Eugenol nanocapsule for enhanced therapeutic activity against periodontal infections.
        Journal of drug targeting. 2016; 24: 24-33
        • Lin JH
        • Feng F
        • Yu MC
        • Wang CH
        • Chang PC.
        Modulation of periodontitis progression using pH-responsive nanosphere encapsulating metronidazole or N-phenacylthialzolium bromide.
        Journal of periodontal research. 2018; 53: 22-28
        • Yadav N
        • Nanda S
        • Sharma G
        • Katare O.
        Systematically optimized ketoprofen-loaded novel proniosomal formulation for periodontitis: in vitro characterization and in vivo pharmacodynamic evaluation.
        AAPS PharmSciTech. 2017; 18: 1863-1880
        • Chang PC
        • Chao YC
        • Hsiao MH
        • et al.
        Inhibition of periodontitis induction using a stimuli-responsive hydrogel carrying naringin.
        Journal of periodontology. 2017; 88: 190-196
        • Yu MC
        • Chang CY
        • Chao YC
        • et al.
        pH-Responsive hydrogel with an anti-glycation agent for modulating experimental periodontitis.
        Journal of periodontology. 2016; 87: 742-748
        • Wang B
        • Booij-Vrieling HE
        • Bronkhorst EM
        • et al.
        Antimicrobial and anti-inflammatory thermo-reversible hydrogel for periodontal delivery.
        Acta biomaterialia. 2020; 116: 259-267
        • Meenakshi SS
        • Sankari M.
        Effectiveness of chitosan nanohydrogel as a bone regenerative material in intrabony defects in patients with chronic periodontitis: a randomized clinical trial.
        Journal of advanced oral research. 2021; (2320206821998574)
        • Shaheen MA
        • Elmeadawy SH
        • Bazeed FB
        • Anees MM
        • Saleh NM.
        Innovative coenzyme Q 10-loaded nanoformulation as an adjunct approach for the management of moderate periodontitis: preparation, evaluation, and clinical study.
        Drug delivery and translational research. 2020; 10: 548-564
        • Abnet CC
        • Arnold M
        • Wei W-Q.
        Epidemiology of esophageal squamous cell carcinoma.
        Gastroenterology. 2018; 154: 360-373
        • Leemans CR
        • Braakhuis BJ
        • Brakenhoff RH.
        The molecular biology of head and neck cancer.
        Nature reviews cancer. 2011; 11: 9
        • Bagan J
        • Sarrion G
        • Jimenez Y.
        Oral cancer: clinical features.
        Oral oncology. 2010; 46: 414-417
        • Morita M
        • Kumashiro R
        • Kubo N
        • et al.
        Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention.
        International journal of clinical oncology. 2010; 15: 126-134
        • Wang Y
        • Wan G
        • Li Z
        • et al.
        PEGylated doxorubicin nanoparticles mediated by HN-1 peptide for targeted treatment of oral squamous cell carcinoma.
        International journal of pharmaceutics. 2017; 525: 21-31
        • Wang D
        • Xu X
        • Zhang K
        • et al.
        Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles-polymerpolyethylenimine to improve oral squamous carcinoma treatment.
        International journal of nanomedicine. 2018; 13: 187
        • Chen Y
        • Zhang W
        • Huang Y
        • Gao F
        • Fang X.
        In vivo biodistribution and anti-tumor efficacy evaluation of doxorubicin and paclitaxel-loaded pluronic micelles decorated with c (RGDyK) peptide.
        PloS one. 2016; 11: e0149952
        • Will OM
        • Purcz N
        • Chalaris A
        • et al.
        Increased survival rate by local release of diclofenac in a murine model of recurrent oral carcinoma.
        International journal of nanomedicine. 2016; 11: 5311
        • Figueiró Longo J
        • Muehlmann L
        • Velloso N
        • Simioni A
        • Lozzi S
        Effects of photodynamic therapy mediated by liposomal aluminum-phthalocyanine chloride on chemically induced tongue tumors.
        Chemotherapy. 2012; 1: 2
        • Yang G
        • Yang T
        • Zhang W
        • Lu M
        • Ma X
        • Xiang G.
        In vitro and in vivo antitumor effects of folate-targeted ursolic acid stealth liposome.
        Journal of agricultural and food chemistry. 2014; 62: 2207-2215
        • Li M
        • Li Z
        • Li J
        • et al.
        Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19.
        Molecular medicine reports. 2015; 12: 8185-8192
        • Mazzarino L
        • Loch-Neckel G
        • Bubniak LDS
        • et al.
        Curcumin-loaded chitosan-coated nanoparticles as a new approach for the local treatment of oral cavity cancer.
        Journal of nanoscience and nanotechnology. 2015; 15: 781-791
        • Xiong J
        • Feng J
        • Qiu 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.
        International journal of pharmaceutics. 2019; 554: 93-104
        • Shi X-L
        • Li Y
        • Zhao L-M
        • Su L-W
        • Ding G.
        Delivery of MTH1 inhibitor (TH287) and MDR1 siRNA via hyaluronic acid-based mesoporous silica nanoparticles for oral cancers treatment.
        Colloids and surfaces B: biointerfaces. 2019; 173: 599-606
        • Lin M
        • Wang D
        • Liu S
        • et al.
        Cupreous complex-loaded chitosan nanoparticles for photothermal therapy and chemotherapy of oral epithelial carcinoma.
        ACS applied materials & interfaces. 2015; 7: 20801-20812
        • Shi S
        • Zhang L
        • Zhu M
        • et al.
        Reactive oxygen species-responsive nanoparticles based on peglated prodrug for targeted treatment of oral tongue squamous cell carcinoma by combining photodynamic therapy and chemotherapy.
        ACS applied materials & interfaces. 2018; 10: 29260-29272
        • Chen X-J
        • Zhang X-Q
        • Tang M-X
        • Liu Q
        • Zhou G.
        Anti-PD-L1-modified and ATRA-loaded nanoparticles for immuno-treatment of oral dysplasia and oral squamous cell carcinoma.
        Nanomedicine. 2020; 15: 951-968
        • Al Mubarak S
        • Robert AA
        • Baskaradoss JK
        • et al.
        The prevalence of oral Candida infections in periodontitis patients with type 2 diabetes mellitus.
        Journal of infection and public health. 2013; 6: 296-301
        • Maheronnaghsh M
        • Tolouei S
        • Dehghan P
        • Chadeganipour M
        • Yazdi M.
        Identification of Candida species in patients with oral lesion undergoing chemotherapy along with minimum inhibitory concentration to fluconazole.
        Advanced biomedical research. 2016; 5
        • Millsop JW
        • Fazel N.
        Oral candidiasis.
        Clinics in dermatology. 2016; 34: 487-494
        • McCarthy GM.
        Host factors associated with HIV-related oral candidiasis: a review.
        Oral surgery, oral medicine, oral pathology. 1992; 73: 181-186
        • Sharon V
        • Fazel N.
        Oral candidiasis and angular cheilitis.
        Dermatologic therapy. 2010; 23: 230-242
        • Tonglairoum P
        • Ngawhirunpat T
        • Rojanarata T
        • Panomsuk S
        • Kaomongkolgit R
        • Opanasopit P.
        Fabrication of mucoadhesive chitosan coated polyvinylpyrrolidone/cyclodextrin/clotrimazole sandwich patches for oral candidiasis.
        Carbohydrate polymers. 2015; 132: 173-179
        • Kong EF
        • Tsui C
        • Boyce H
        • et al.
        Development and in vivo evaluation of a novel histatin-5 bioadhesive hydrogel formulation against oral candidiasis.
        Antimicrobial agents and chemotherapy. 2016; 60: 881-889
        • Zia Q
        • Khan AA
        • Swaleha Z
        • Owais M.
        Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans.
        International journal of nanomedicine. 2015; 10: 1769
        • Zhou L
        • Zhang P
        • Chen Z
        • et al.
        Preparation, characterization, and evaluation of amphotericin B-loaded MPEG-PCL-g-PEI micelles for local treatment of oral Candida albicans.
        International journal of nanomedicine. 2017; 12: 4269
        • Gajdošová M
        • Vetchý D
        • Muselík J
        • et al.
        Bilayer mucoadhesive buccal films with prolonged release of ciclopirox olamine for the treatment of oral candidiasis: in vitro development, ex vivo permeation testing, pharmacokinetic and efficacy study in rabbits.
        International journal of pharmaceutics. 2021; 592: 120086
        • Soriano-Ruiz JL
        • Calpena-Capmany AC
        • Cañadas-Enrich C
        • et al.
        Biopharmaceutical profile of a clotrimazole nanoemulsion: evaluation on skin and mucosae as anticandidal agent.
        International journal of pharmaceutics. 2019; 554: 105-115
        • Rençber S
        • Karavana SY
        • Yılmaz FF
        • et al.
        Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis.
        International journal of nanomedicine. 2016; 11: 2641
        • Alkhalidi HM
        • Hosny KM
        • Rizg WY.
        Oral gel loaded by fluconazole‒sesame oil nanotransfersomes: development, optimization, and assessment of antifungal activity.
        Pharmaceutics. 2021; 13: 27
        • Hopcraft M
        • Tan C.
        Xerostomia: an update for clinicians.
        Australian dental journal. 2010; 55: 238-244
        • Ohara Y
        • Hirano H
        • Yoshida H
        • et al.
        Prevalence and factors associated with xerostomia and hyposalivation among community-dwelling older people in Japan.
        Gerodontology. 2016; 33: 20-27
        • Niklander S
        • Veas L
        • Barrera C
        • Fuentes F
        • Chiappini G
        • Marshall M.
        Risk factors, hyposalivation and impact of xerostomia on oral health-related quality of life.
        Brazilian oral research. 2017; : 31
        • Almeida JP
        • Kowalski LP.
        Pilocarpine used to treat xerostomia in patients submitted to radioactive iodine therapy: a pilot study.
        Brazilian journal of otorhinolaryngology. 2010; 76: 659-662
        • Gómez-Moreno G
        • Aguilar-Salvatierra A
        • Guardia J
        • et al.
        The efficacy of a topical sialogogue spray containing 1% malic acid in patients with antidepressant-induced dry mouth: a double-blind, randomized clinical trial.
        Depression and anxiety. 2013; 30: 137-142
        • Muthumariappan S
        • Ng WC
        • Adine C
        • et al.
        Localized delivery of pilocarpine to hypofunctional salivary glands through electrospun nanofiber mats: an ex vivo and in vivo study.
        International journal of molecular sciences. 2019; 20: 541
        • Heiser C
        • Hofauer B
        • Scherer E
        • Schukraft J
        • Knopf A.
        Liposomal treatment of xerostomia, odor, and taste abnormalities in patients with head and neck cancer.
        Head & neck. 2016; 38: E1232-E1237
        • Scully C
        • Carrozzo M.
        Oral mucosal disease: Lichen planus.
        British journal of oral and maxillofacial surgery. 2008; 46: 15-21
        • Munde AD
        • Karle RR
        • Wankhede PK
        • Shaikh SS
        • Kulkurni M.
        Demographic and clinical profile of oral lichen planus: a retrospective study.
        Contemporary clinical dentistry. 2013; 4: 181
        • Shirasuna K.
        Oral lichen planus: malignant potential and diagnosis.
        Oral science international. 2014; 11: 1-7
        • Gupta S
        • Jawanda MK.
        Oral lichen planus: an update on etiology, pathogenesis, clinical presentation, diagnosis and management.
        Indian journal of dermatology. 2015; 60: 222
        • Kuo R-C
        • Lin H-P
        • Sun A
        • Wang Y-P.
        Prompt healing of erosive oral lichen planus lesion after combined corticosteroid treatment with locally injected triamcinolone acetonide plus oral prednisolone.
        Journal of the Formosan Medical Association. 2013; 112: 216-220
        • Preeti L
        • Magesh K
        • Rajkumar K
        • Karthik R.
        Recurrent aphthous stomatitis.
        Journal of oral and maxillofacial pathology. 2011; 15: 252
        • Chavan M
        • Jain H
        • Diwan N
        • Khedkar S
        • Shete A
        • Durkar S.
        Recurrent aphthous stomatitis: a review.
        Journal of oral pathology & medicine. 2012; 41: 577-583
        • Ślebioda Z
        • Szponar E
        • Kowalska A.
        Recurrent aphthous stomatitis: genetic aspects of etiology.
        Advances in dermatology and allergology/Postȩpy Dermatologii I Alergologii. 2013; 30: 96
        • Tarakji B
        • Gazal G
        • Al-Maweri SA
        • Azzeghaiby SN
        • Alaizari N.
        Guideline for the diagnosis and treatment of recurrent aphthous stomatitis for dental practitioners.
        Journal of international oral health. 2015; 7: 74
        • Colley H
        • Said Z
        • Santocildes-Romero M
        • et al.
        Pre-clinical evaluation of novel mucoadhesive bilayer patches for local delivery of clobetasol-17-propionate to the oral mucosa.
        Biomaterials. 2018; 178: 134-146
        • Arafa MG
        • Ghalwash D
        • El-Kersh DM
        • Elmazar M.
        Propolis-based niosomes as oromuco-adhesive films: a randomized clinical trial of a therapeutic drug delivery platform for the treatment of oral recurrent aphthous ulcers.
        Scientific reports. 2018; 8: 18056
        • Raber-Durlacher JE
        • Elad S
        • Barasch A.
        Oral mucositis.
        Oral oncology. 2010; 46: 452-456
        • Chaveli-López B
        • Bagán-Sebastián JV.
        Treatment of oral mucositis due to chemotherapy.
        Journal of clinical and experimental dentistry. 2016; 8: e201
        • Berger K
        • Schopohl D
        • Bollig A
        • et al.
        Burden of oral mucositis: a systematic review and implications for future research.
        Oncology research and treatment. 2018; 41: 399-405
        • 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 and surfaces B: biointerfaces. 2018; 167: 468-473
        • Rezazadeh M
        • Jafari N
        • Akbari V
        • et al.
        A mucoadhesive thermosensitive hydrogel containing erythropoietin as a potential treatment in oral mucositis: in vitro and in vivo studies.
        Drug delivery and translational research. 2018; 8: 1226-1237
        • Qataya PO
        • Elsayed NM
        • Elguindy NM
        • Ahmed Hafiz M
        • Samy WM
        Selenium: a sole treatment for erosive oral lichen planus (randomized controlled clinical trial).
        Oral diseases. 2020; 26: 789-804
        • El-Wakeel NM
        • Dawoud MH.
        Topical insulin-liposomal formulation in management of recurrent aphthous ulcers: a randomized placebo-controlled trial.
        Journal of investigative and clinical dentistry. 2019; : e12437
        • Shao Y
        • Zhou H.
        Clinical evaluation of an oral mucoadhesive film containing chitosan for the treatment of recurrent aphthous stomatitis: a randomized, double-blind study.
        Journal of dermatological treatment. 2020; 31: 739-743
        • Karavana SY
        • Gökçe EH
        • Rençber S
        • et al.
        A new approach to the treatment of recurrent aphthous stomatitis with bioadhesive gels containing cyclosporine A solid lipid nanoparticles: in vivo/in vitro examinations.
        International journal of nanomedicine. 2012; 7: 5693
        • Choi JS
        • Han SH
        • Hyun C
        • Yoo HS.
        Buccal adhesive nanofibers containing human growth hormone for oral mucositis.
        Journal of biomedical materials research part B: applied biomaterials. 2016; 104: 1396-1406
        • Velez I
        • Spielholz NI
        • Siegel MA
        • Gonzalez T.
        MuGard, an oral mucoadhesive hydrogel, reduces the signs and symptoms of oral mucositis in patients with lichen planus: a double-blind, randomized, placebo-controlled pilot study.
        Oral surgery, oral medicine, oral pathology and oral radiology. 2014; 118 (e652): 657-664
        • Elhadad MA
        • El-Negoumy E
        • Taalab MR
        • Ibrahim RS
        • Elsaka RO.
        The effect of topical chamomile in the prevention of chemotherapy-induced oral mucositis: a randomized clinical trial.
        Oral Diseases. 2020;
        • Enin HAA
        • El Nabarawy NA
        • Elmonem RAA.
        Treatment of radiation-induced oral mucositis using a novel accepted taste of prolonged release mucoadhesive Bi-medicated double-layer buccal films.
        AAPS PharmSciTech. 2017; 18: 563-575
        • Azizi A
        • Dadras OG
        • Jafari M
        • Ghadim NM
        • Lawaf S
        • Sadri D.
        Efficacy of 0.1% triamcinolone with nanoliposomal carrier formulation in orabase for oral lichen planus patients: a clinical trial.
        European journal of integrative medicine. 2016; 8: 275-280
        • Rossi S
        • Sandri G
        • Caramella CM.
        Buccal drug delivery: a challenge already won?.
        Drug discovery today: technologies. 2005; 2: 59-65