In Vitro Bioactivities of Alcohol-Free Benzydamine Oromucosal Solutions

Authors

  • Suwipa Ungphaiboon Department of Pharmaceutical Technology and Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
  • Sutasinee Ardhanwanich Department of Pharmaceutical Technology and Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
  • Sonsawan Kongpuckdee Department of Thai Traditional Medicine, Faculty of Health and Sports Science, Thaksin University, Pa Phayom, Phatthalung 93210, Thailand.
  • Duangkhae Maneenuan Department of Pharmaceutical Technology and Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
  • Teerapol Srichana Department of Pharmaceutical Technology and Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.

DOI:

https://doi.org/10.31584/jhsmr.20231002

Keywords:

alcohol-free, benzydamine, bioactivity, chitosan, poloxamer 407, oromucosal solution

Abstract

Objective: This research aimed to evaluate the effects of chitosan and poloxamer 407 on in vitro cytotoxicity, antiinflammatory, wound healing, and antimicrobial activities of 0.3% w/v benzydamine hydrochloride (HCl) oromucosal solutions.
Material and Methods: The effects of three alcohol-free benzydamine HCl oromucosal formulations; containing: 1) 0.5% w/v chitosan, 2) 15% w/v poloxamer 407, and 3) a combination of 0.5% w/v chitosan and 15% w/v poloxamer 407, on in vitro cytotoxicity and biological activities were evaluated and compared to a commercial benzydamine HCl mouth spray, containing alcohol and 0.12% chlorhexidine solution.
Results: All alcohol-free benzydamine HCl formulations and their vehicles were less cytotoxic to the macrophage RAW 264.7 cell line than the commercial spray and to the human gingival fibroblast cell line than chlorhexidine, respectively. The formulation containing 0.5% w/v chitosan exhibited the highest wound healing activity on the fibroblast cells among all tested products, and showed anti-inflammatory activity on macrophage cells, which is comparable to benzydamine HCl. Furthermore, from the time-kill assay, this formulation completely inhibited Streptococcus mutans within 1 minute, similar to 0.12% chlorhexidine solution, and reduced the cell number of Candida albicans more rapidly than the commercial spray.
Conclusion: The alcohol-free benzydamine HCl solution containing 0.5% w/v chitosan as a mucoadhesive polymer is a promising oral care candidate, which is safe to be used, and has wound healing, anti inflammatory, and antimicrobial activities.

References

Brown TJ, Gupta A. Management of cancer therapy-associated oral mucositis. JCO Oncol Pract 2020;16:103–9.

Roopashri G, Jayanthi K, Guruprasad R. Efficacy of benzydamine hydrochloride, chlorhexidine, and povidone iodine in the treatment of oral mucositis among patients undergoing radiotherapy in head and neck malignancies: a drug trail. Contemp Clin Dent 2011;2:8–12.

Sheibani KM, Mafi AR, Moghaddam S, Taslimi F, Amiran A, Ameri A. Efficacy of benzydamine oral rinse in prevention and management of radiation-induced oral mucositis: A doubleblind placebo-controlled randomized clinical trial. Asia Pac J Clin Oncol 2015;11:22–7.

Vivek S, Shwetha R. Endogenous pH, titratable acidity of commercially available mouthwashes in Indian market. Int J Clin Trials 2015;2:20-4.

Karavana (Hızarcıoğlu) SY, Sezer B, Güneri P, Veral A, Boyacioğlu H, Ertan G, et al. Efficacy of topical benzydamine hydrochloride gel on oral mucosal ulcers: an in vivo animal study. Int J Oral Maxillofac Surg 2011;40:973–8.

Fatullayeva S, Tagiyev D, Zeynalov N, Mammadova S, Aliyeva E. Recent advances of chitosan-based polymers in biomedical applications and environmental protection. J Polym Res 2022;29:259.

Carlson RP, Taffs R, Davison WM, Stewart PS. Anti-biofilm properties of chitosan-coated surfaces. J Biomater Sci Polym Ed 2008;19:1035–46.

Costa E, Silva S, Tavaria F, Pintado M. Antimicrobial and antibiofilm activity of chitosan on the oral pathogen Candida albicans. Pathogens 2014;3:908–19.

Mahattanadul S, Mustafa MW, Kuadkaew S, Pattharachayakul S, Ungphaiboon S, Sawanyawisuth K. Oral ulcer healing and anti-Candida efficacy of an alcohol-free chitosan-curcumin mouthwash. Eur Rev Med Pharmacol Sci 2018;22:7020–3.

Mahima VG, Patil K, Kulkarni PK, Tayal S, Keshari D. Use of chitosan mouth-wash in radio-chemotherapy induced oral mucositis: A case-control study. J Adv Clin Res Insights 2015;2:248–52.

Pasquantonio G, Greco C, Prenna M, Ripa C, Vitali LA, Petrelli D, et al. Antibacterial activity and anti-biofilm effect of chitosan against strains of Streptococcus mutans isolated in dental plaque. Int J Immunopathol Pharmacol 2008;21:993–7.

Arancibia R, Maturana C, Silva D, Tobar N, Tapia C, Salazar JC, et al. Effects of chitosan particles in periodontal pathogens and gingival fibroblasts. J Dent Res 2013;92:740–5.

Paul W, Sharma C, Tirunal C. Chitosan and alginate wound dressings: a short review. Trends in biomaterials & artificial organs [serial on the Internet]. 2004 [cited 2023 May 2]; Available from: https://www.semanticscholar.org/paper/Chitosan-and-Alginate-Wound-Dressings%3A-A-Short-Paul-Sharma/b38c2de711be7a10a802c8534a7879b6801186ef

Bansal M, Mittal N, Yadav SK, Khan G, Gupta P, Mishra B, et al. Periodontal thermoresponsive, mucoadhesive dual antimicrobial loaded in-situ gel for the treatment of periodontal disease: Preparation, in-vitro characterization and antimicrobial study. J Oral Biol Craniofac Res 2018;8:126–33.

Sarideechaigul W, Ungphaiboon S, Ardpolthai H, Jehsama-ae A, Sangsuttiwongsa K, Taweechaisupapong S. Effect of oral moisturizers containing chitosan and poloxamer 407 on biofilm formation of Candida species and Streptococcus mutans: in vitro. Songklanakarin J Sci Technol 2022;44:1298–305.

Tewtrakul S, Tansakul P, Panichayupakaranant P. Effects of rhinacanthins from Rhinacanthus nasutus on nitric oxide, prostaglandin E2 and tumor necrosis factor-alpha releases using RAW264.7 macrophage cells. Phytomedicine 2009;16:581–5.

Chaitrakoonthong T, Ampornaramveth R, Kamolratanakul P. Rinsing with l-ascorbic acid exhibits concentration-dependent effects on human gingival fibroblast in vitro wound healing behavior. Int J Dent 2020;2020:4706418.

Sungkharak S, Ungphaiboon S. Antibacterial activity against acne involved bacteria of chitosan in a soluble state and as nanoparticles. Chiang Mai J Sci 2016;43:1150–9.

Perumal S, Mahmud R. Chemical analysis, inhibition of biofilm formation and biofilm eradication potential of Euphorbia hirta L. against clinical isolates and standard strains. BMC Complement Altern Med 2013;13:346.

Nittayananta W, Limsuwan S, Srichana T, Sae-Wong C, Amnuaikit T. Oral spray containing plant-derived compounds is effective against common oral pathogens. Arch. Oral Biol 2018;90:80–5.

Dai T, Tanaka M, Huang YY, Hamblin MR. Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects. Expert Rev Anti Infect Ther 2011;9:857–79.

Hurler J, Skalko-Basnet N. Potentials of chitosan-based delivery systems in wound therapy: bioadhesion study. J Funct Biomater 2012;3:37–48.

Liu H, Wang C, Li C, Qin Y, Wang Z, Yang F, et al. A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. RSC Adv 2018;8:7533–49.

Werner CW de A, Seymour RA. Are alcohol containing mouthwashes safe? Br Dent J 2009;207:E19.

Haghgoo R, Abbasi F. Evaluation of the use of a peppermint mouth rinse for halitosis by girls studying in Tehran high schools. J Int Soc Prev Community Dent 2013;3:29–31.

Radu CM, Radu CC, BochiŞ SA, ArbănaŞi EM, Lucan AI, Murvai VR, et al. Revisiting the therapeutic effects of essential oils on the oral microbiome. Pharmacy 2023;11:33.

Prasanna SGV, Lakshmanan DR. Characteristics, uses and side effects of chlorhexidine-A review. IOSR J Dent Med Sci 2016;15:57–9.

Rossi S, Marciello M, Bonferoni MC, Ferrari F, Sandri G, Dacarro C, et al. Thermally sensitive gels based on chitosan derivatives for the treatment of oral mucositis. Eur J Pharm Biopharm 2010;74:248–54.

Aranaz I, Acosta N, Civera C, Elorza B, Mingo J, Castro C, et al. Cosmetics and cosmeceutical applications of chitin, chitosan and their derivatives. Polymers 2018;10:213.

Gomaa EZ. Improvement of antimicrobial and anti-biofilm potentials of mouthwashes by chitosan produced by lactic acid bacteria: an in vitro study. J Microbiol Biotechnol 2017;2:52-7.

Rabea EI, Badawy MET, Stevens CV, Smagghe G, Steurbaut W. Chitosan as antimicrobial agent: applications and mode of action. Biomacromolecules 2003;4:1457–65.

Downloads

Published

2023-11-20

How to Cite

1.
Ungphaiboon S, Ardhanwanich S, Kongpuckdee S, Maneenuan D, Srichana T. In Vitro Bioactivities of Alcohol-Free Benzydamine Oromucosal Solutions. J Health Sci Med Res [Internet]. 2023 Nov. 20 [cited 2024 Dec. 23];42(1):e20231002. Available from: https://he01.tci-thaijo.org/index.php/jhsmr/article/view/267195

Issue

Section

Original Article