Advances in Adhesive Drug Delivery for Recurrent Aphthous Ulcers

doi:10.12337/zgkqjxjyzz.2025.06.003

Chinese Journal of Stomatological Continuing Education ›› 2025, Vol. 28 ›› Issue (6): 393-397.DOI: 10.12337/zgkqjxjyzz.2025.06.003

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Advances in Adhesive Drug Delivery for Recurrent Aphthous Ulcers

Xiaoju Chen¹, Zhongfang Zhao^2,*, Xiaohan He³, Bin Liu^1,*

¹Department of Prosthodontics, School / Hospital of Stomatology Lanzhou University;
²Department of Periodontology and Mucosal Diseases, School / Hospital of Stomatology Lanzhou University;
³Department of Orthodontics, School / Hospital of Stomatology Lanzhou University, Lanzhou, P.R. China

Online:2025-11-30 Published:2025-11-30
Contact: Zhongfang Zhao. Tel: 0931-7716666. Email: zzfkq2015@126.com. Address: No. 199, Donggang West Road, Chengguan District, Lanzhou 730000, Gansu Province, P.R. China; Bin Liu. Tel: 0931-8915003. Email: liubkq@lzu.edu.cn. Address: No. 199, Donggang West Road, Chengguan District, Lanzhou 730000, Gansu Province, P.R. China.
Supported by:
Major Project of the Joint Research Fund of Gansu Province (No.24JRRA941); Joint Fund Project of Gansu Province (No.24JRRA943); The Youth Fund Project of Lanzhou University School and Hospital of Stomatology (No.lzukqky-2022-t10)

Abstract

Abstract: Recurrent aphthous ulcer (RAU) is a prevalent oral mucosal disorder characterized by painful, recurrent round or oval-shaped ulcers. Treatment aims to reduce recurrence frequency, alleviate pain, and accelerate healing. Local therapy is the mainstay, among which adhesive oral mucosal drug delivery systems are promising for targeted and prolonged drug action. This review summarizes advances in such systems for RAU treatment, including flexible films, patches, and microneedle patches. It analyzes the design strategies and advantages of these systems, and points out their shortcomings, with the aim of providing ideas and inspiration for further research.

Key words: recurrent aphthous ulcer, wet adhesion, oral local drug delivery, hydrogel, microneedle patch

Xiaoju Chen, Zhongfang Zhao, Xiaohan He, Bin Liu. Advances in Adhesive Drug Delivery for Recurrent Aphthous Ulcers[J]. Chinese Journal of Stomatological Continuing Education, 2025, 28(6): 393-397.

References

[1] Conejero Del Mazo R, García Forcén L, Navarro Aguilar ME. Recurrent aphthous stomatitis[J]. Med Clin (Barc), 2023, 161(6):251-259.
[2] Yu Y, Gao Y, Zeng Y, et al.Multifunctional hyaluronic acid/gelatin methacryloyl core-shell microneedle for comprehensively treating oral mucosal ulcers[J]. Int J Biol Macromol, 2024, 266(Pt 1):131221.
[3] Randall DA, Wilson Westmar NL, Neville BW.Common oral lesions[J]. Am Fam Physician, 2022, 105(4):369-376.
[4] Seyyedi SA, Sanatkhani M, Pakfetrat A, et al.The therapeutic effects of chamomilla tincture mouthwash on oral aphthae: A Randomized Clinical Trial[J]. J Clin Exp Dent, 2014, 6(5):e535-538.
[5] Liu C, Zhou Z, Liu G, et al.Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration[J]. Am J Med, 2012, 125(3):292-301.
[6] Mansour G, Ouda S, Shaker A, et al.Clinical efficacy of new aloe vera- and myrrh-based oral mucoadhesive gels in the management of minor recurrent aphthous stomatitis: a randomized, double-blind, vehicle-controlled study[J]. J Oral Pathol Med, 2014, 43(6):405-409.
[7] Zhu S, Shi Q, Lu J. Curative effect of oral ulcer powder on the treatment of recurrent aphthous ulcer[J]. Pak J Pharm Sci, 2018, 31(3(Special)):1175-1178.
[8] 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[J]. J Dermatolog Treat, 2020, 31(7):739-743.
[9] Špiljak B, Somogyi Škoc M, Rezić Meštrović I, et al.Targeting the oral mucosa: emerging drug delivery platforms and the therapeutic potential of glycosaminoglycans[J]. Pharmaceutics, 2025, 17(9):1212.
[10] Arafa MG, Ghalwash D, El-kersh DM, et al. Publisher Correction: 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[J]. Sci Rep, 2020, 10(1):2459.
[11] Daněk Z, Gajdziok J, Doležel P, et al.Buccal films as a dressing for the treatment of aphthous lesions[J]. J Oral Pathol Med, 2017, 46(4):301-306.
[12] Rodu B, Russell CM.Performance of a hydroxypropyl cellulose film former in normal and ulcerated oral mucosa[J]. Oral Surg Oral Med Oral Pathol, 1988, 65(6): 699-703.
[13] Ofluoglu D, Ergun S, Warnakulasuriya S, et al.An evaluation of the efficacy of a topical gel with Triester Glycerol Oxide (TGO) in the treatment of minor recurrent aphthous stomatitis in a Turkish cohort: A randomized, double-blind, placebo-controlled clinical trial[J]. Med Oral Patol Oral Cir Bucal, 2017, 22(2):e159-e166.
[14] Fernandes Teixeira FM, Figueiredo Pereira M, Gomes Ferreira NL, et al.Spongy film of cellulosic polysaccharide as a dressing for aphthous stomatitis treatment in rabbits[J]. Acta Cir Bras, 2014, 29(4):231-236.
[15] Yotsuyanagi T, Yamamura K, Akao Y.Mucosa-adhesive film containing local analgesic[J]. Lancet, 1985, 2(8455):613.
[16] Alhallak M, Karpukhina N, Patel M.Permeability of triamcinolone acetonide, released from mucoadhesive films, through a buccal mucosa-mimetic barrier: Permeapad™[J]. Dent Mater, 2024, 40(9):1372-1377.
[17] Cao X, Wu B, Chen J, et al.Hydroxypropyl cellulose-based orally dissolving film loaded with insoluble dexamethasone for treatment of oral ulcers[J]. Mol Pharm, 2024, 21(8):4012-4023.
[18] Farid RM, Wen MM.Promote recurrent aphthous ulcer healing with low dose prednisolone bilayer mucoadhesive buccal film[J]. Curr Drug Deliv, 2017, 14(1):123-135.
[19] Chang Y, Zhao W, Li W, et al.Bioadhesive and drug-loaded cellulose nanofiber/alginate film for healing oral mucosal wounds[J]. Int J Biol Macromol, 2024, 276(Pt 1): 133858.
[20] Karavana Hizarcioğlu SY, Sezer B, Güneri P, et al.Efficacy of topical benzydamine hydrochloride gel on oral mucosal ulcers: an in vivo animal study[J]. Int J Oral Maxillofac Surg, 2011, 40(9):973-978.
[21] Wang X, Xiong Y, Zheng X, et al.Preparation of capsaicin-loaded ultrafine fiber film and its application in the treatment of oral ulcers in rats[J]. Sci Rep, 2023, 13(1): 13941.
[22] Shady NH, Altemani AH, Altemani FH, et al.The potential of Corchorus olitorius seeds buccal films for treatment of recurrent minor aphthous ulcerations in human volunteers[J]. Molecules, 2022, 27(20):7020.
[23] Yan Y, Liu T, Tian X, et al.A double-layer thin oral film for wet oral mucosa adhesion and efficient treatment of oral ulcers[J]. J Mater Chem B, 2024, 12(12):3015-3021.
[24] Ge H, Yu J, Pan L, et al.A bioadhesive sustained-release films for in situ therapy of oral ulcers[J]. Mater Des, 2025, 259:114765.
[25] Lee J, Shin D, Roh JL.Treatment of intractable oral ulceration with an oral mucosa equivalent[J]. J Biomed Mater Res B Appl Biomater, 2019, 107(6): 1779-1785.
[26] Xing J, Ding Y, Zheng X, et al.Barnacle-inspired robust and aesthetic Janus patch with instinctive wet adhesive for oral ulcer treatment[J]. Chem Eng J, 2022, 444: 136580.
[27] Fu H, Yang J, Shen Z, et al.Antibacterial, wet adhesive, and healing-promoting nanosheets for the treatment of oral ulcers[J]. Biomater Sci, 2023, 11(9):3214-3226.
[28] Carvalho JPF, Silva ACQ, Bastos V, et al.Nanocellulose-based patches loaded with hyaluronic acid and diclofenac towards aphthous stomatitis treatment[J]. Nanomaterials(Basel), 2020, 10(4):628.
[29] Wang Y, Pan Z, Cui J, et al.Adhesive hydrogel releases protocatechualdehyde-Fe(3+) complex to promote three healing stages for accelerated therapy of oral ulcers[J]. Acta Biomater, 2024, 178:68-82.
[30] Colley HE, Said Z, Santocildes-romero ME, et al. Pre-clinical evaluation of novel mucoadhesive bilayer patches for local delivery of clobetasol-17-propionate to the oral mucosa[J]. Biomaterials, 2018, 178:134-146.
[31] Wu DT, Freedman BR, Vining KH, et al.Tough adhesive hydrogel for intraoral adhesion and drug delivery[J]. J Dent Res, 2023, 102(5):497-504.
[32] Chen H, Li X, Gong Y, et al.Unidirectional drug release from 3D printed personalized buccal patches using FDM technology[J]. Int J Pharm, 2023, 645:123382.
[33] Dou X, Li G, Wang S, et al.Probiotic-loaded calcium alginate/fucoidan hydrogels for promoting oral ulcer healing[J]. Int J Biol Macromol, 2023, 244:125273.
[34] Edmans JG, Ollington B, Colley HE, et al.Electrospun patch delivery of anti-TNFα F(ab) for the treatment of inflammatory oral mucosal disease[J]. J Control Release, 2022, 350:146-157.
[35] Laffleur F, Küppers P.Adhesive alginate for buccal delivery in aphthous stomatitis[J]. Carbohydr Res, 2019, 477:51-57.
[36] Zhang Y, Liu L, Yu X, et al.A bio-inspired Janus hydrogel patch facilitates oral ulcer repair by combining prolonged wet adhesion and lubrication[J]. Acta Biomater, 2024, 190:120-132.
[37] Ryu JH, Choi JS, Park E, et al.Chitosan oral patches inspired by mussel adhesion[J]. J Control Release, 2020, 317:57-66.
[38] Cheng H, Tian G, Liu H, et al.A molybdenum sulfide based nitric oxide controlled release oral gel for rapid healing of oral mucosal ulcers[J]. J Colloid Interface Sci, 2025, 678(Pt A):560-571.
[39] Donnelly RF, Raj Singh TR, Woolfson AD.Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety[J]. Drug Deliv, 2010, 17(4):187-207.
[40] Li Y, Bi D, Hu Z, et al.Hydrogel-forming microneedles with applications in oral diseases management[J]. Materials (Basel), 2023, 16(13):4805.
[41] Peng K, Vora LK, Domínguez-robles J, et al. Hydrogel-forming microneedles for rapid and efficient skin deposition of controlled release tip-implants[J]. Mater Sci Eng C Mater Biol Appl, 2021, 127:112226.
[42] Donnelly RF, Morrow DI, Mccrudden MT, et al.Hydrogel-forming and dissolving microneedles for enhanced delivery of photosensitizers and precursors[J]. Photochem Photobiol, 2014, 90(3):641-647.
[43] Gill HS, Denson DD, Burris BA, et al.Effect of microneedle design on pain in human volunteers[J]. Clin J Pain, 2008, 24(7):585-594.
[44] Di Carla Santos S, Fávaro-moreira NC, Abdalla HB, et al. A crossover clinical study to evaluate pain intensity from microneedle insertion in different parts of the oral cavity[J]. Int J Pharm, 2021, 592:120050.
[45] Yin Z, Zhang X, Bai Y, et al.Dissolvable and layered microneedles composed of hyaluronate/rbFGF/CPC effectively improve the treatment effect on recurrent aphthous ulcers[J]. New J Chem, 2022, 46(15):7279-7289.
[46] Zeng Y, Gao Y, He L, et al.Multifunctional polysaccharide composited microneedle for oral ulcers healing[J]. Mater Today Bio, 2023, 22:100782.
[47] Ge W, Gao Y, He L, et al.Combination therapy using multifunctional dissolvable hyaluronic acid microneedles for oral ulcers[J]. Int J Biol Macromol, 2023, 251: 126333.
[48] Guo X, Zhu T, Yu X, et al.Betamethasone-loaded dissolvable microneedle patch for oral ulcer treatment[J]. Colloids Surf B Biointerfaces, 2023, 222:113100.
[49] Qu X, Guo X, Zhu T, et al.Microneedle patches containing mesoporous polydopamine nanoparticles loaded with triamcinolone acetonide for the treatment of oral mucositis[J]. Front Bioeng Biotechnol, 2023, 11: 1203709.
[50] Ge W, Gao Y, Zeng Y, et al.Silk fibroin microneedles loaded with lipopolysaccharide-pretreated bone marrow mesenchymal stem cell-derived exosomes for oral ulcer treatment[J]. ACS Appl Mater Interfaces, 2024, 16(29): 37486-37496.

Advances in Adhesive Drug Delivery for Recurrent Aphthous Ulcers

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