Evolution of Drug Delivery Systems for Recurrent Aphthous Stomatitis

Abstract

Recurrent aphthous stomatitis (RAS) is a disease marked by painful oral lesions on the buccal and labial mucosa or tongue. Drug delivery systems (DDS) for RAS include topical forms that manage wound healing, cover the ulcer, and relieve the associated pain. DDS targeting the oral mucosa face a major challenge, especially the short residence times in the mouth due to the effect of “saliva wash-out”, which continually removes the drug. The objective of this review is to study the development of preparation forms and delivery systems of various types and preparations that have been used for RAS management from 1965 until February 2020. There are 20 types of DDS for RAS which were discussed in 62 articles. The preparations were classified into 4 preparation forms: liquid, semi-solid, solid, and miscellaneous. In addition, the ultimate DDS for RAS preparations is the semi-solid forms (41.94%), which include 5 types of DDS are gel, paste, patch, cream, and ointment. This preparation was developed into new preparation form (11.29%), such as adhesive alginates, dentifrice, OraDisc, membranes, bioresorbable plates, pellicles, and gelosomes. Generally, the mucosal drug delivery system is the method of choice in RAS treatment because the ulcer is commonly located in the oral mucosa. In conclusion, these preparations are designed to improve drug delivery and drug activity for the treatment of RAS ulcers. Moreover, almost all of these DDS are topical preparations that use various types of mucoadhesive polymers to increase both residence time in the oral mucosa and pain relief in RAS treatment.

Graphical Abstract

Keywords:

• drug delivery system
• DDS
• recurrent aphthous stomatitis
• RAS
• mucoadhesive
• residence time

Acknowledgments

We would like to thank the Minister of Research and Higher Education, Republic of Indonesia, for funding this study.

Abbreviations

RAS, Recurrent Aphthous Stomatitis; DDS, Drug Delivery System; TNF-α, Tumor Necrosis Factor alpha (TNF-α); EDAC, 1- ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride; LA, Listerine Antiseptic; MHC, Major Histocompatibility Complex; IL, interleukin; ROS, Reactive Oxygen Species; PDL, Pudilan Xiaoyan Oral Liquid; PKT, Pudilan Keyaning Toothpaste; MC, methylcellulose; CMC, Carboxymethylcellulose; HPEC, Hydroxypropylethylcellulose; HPMC, Hydroxypropylmethylcellulose; SCMC, Sodium carboxymethylcellulose; HA, Hyaluronic Acid; PEG, Polyethylene glycol; HIV, Human Immunodeficiency Virus; SLNs, Solid Lipid Nanoparticles; CsA, Cyclosporine A; iNOS, inducible Nitric Oxide Synthase; bGF, basic Fibroblast Growth Factor; PE, polyethylene; HDPE, high-density polyethylene; LDPE, low-density polyethylene; MDFs, Mouth Dissolved Films; DSP, Dexamethasone Sodium Phosphate; PEO, Polyethylenoxyde; TPP, tripolyphosphate; BMV, Betamethasone-17-valerate; PVP, polyvinylpyrrolidone.

Disclosure

The authors declare no conflicts of interest for this work.

Additional information

Funding

This research was funded by the College Superior Applied Research (Penelitian Terapan Unggulan Perguruan Tinggi) and Doctoral Dissertation Research Grants, Ministry of Culture and Education, Republic of Indonesia, grant number 1207/UN6.3.1/PT.00/2021.