FORMULATION AND OPTIMIZATION OF A GALLIC ACID-LOADED NAIL SERUM USING FACTORIAL DESIGN FOR ENHANCED NAIL DELIVERY
DOI:
https://doi.org/10.22159/ijap.2025v17i6.55068Keywords:
Onychomycosis, Gallic acid, Topical nail serum, Factorial design, L929 fibroblast cellsAbstract
Objective: Onychomycosis is a persistent fungal infection of the nails, and conventional treatments, including oral antifungals, are often associated with systemic side effects, such as hepatotoxicity, and exhibit high recurrence rates. In response to these challenges, the present project aimed to develop a novel gallic acid-loaded nail serum, a unique approach that leverages the antifungal, antioxidant, and anti-inflammatory properties of gallic acid to formulate a safer and more efficacious topical treatment than conventional therapy.
Methods: The formulations were developed using a 2³ factorial design approach to optimize the concentrations of acetone, ethyl acetate, and glycerol for desired viscosity and spreadability. The serum was evaluated for its physical characteristics, viscosity, spreadability, in vitro drug permeation, antifungal activity, and in vitro cytocompatibility using the MTT assay on L929 fibroblast cells, as well as its ex vivo efficacy in a porcine hoof model.
Results: The optimized formulation showed appropriate viscosity (755.67 cP) and spreadability (7.22 cm), along with smooth texture, good gloss, and a pH suitable for nails (pH 5.2–5.4). Drug permeation studies revealed that the serum enhanced gallic acid penetration more than an aqueous solution. Antifungal studies showed a better zone of inhibition (22.0±0.5 mm) compared to a marketed antifungal product. Cytocompatibility studies indicated more than 88% cell viability. Ex vivo analysis confirmed significant fungal clearance on infected hoof models.
Conclusion: The gallic acid-loaded nail serum developed in this study demonstrated effective antifungal activity, enhanced nail penetration, and favorable physical properties, It offers a natural, safe, and patient-friendly alternative to conventional antifungal treatments for onychomycosis, encouraging further clinical research and potential commercial development.
References
1. Litaiem N, Mnif E, Zeglaoui F. Dermoscopy of onychomycosis: a systematic review. Dermatol Pract Concept. 2023 Jan 1;13(1):e2023072. doi: 10.5826/dpc.1301a72, PMID 36892372.
2. Mohsin SA, Shaukat S, Nawaz M, Ur Rehman T, Irshad N, Majid M. Appraisal of selected ethnomedicinal plants as alternative therapies against onychomycosis: evaluation of synergy and time kill kinetics. Front Pharmacol. 2022 Nov 24;13:1067697. doi: 10.3389/fphar.2022.1067697, PMID 36506532.
3. Khan N, Ahmed S, Sheraz MA, Anwar Z, Ahmad I. Pharmaceutical based cosmetic serums. Profiles Drug Subst Excip Relat Methodol. 2023 Jan 1;48:167-210. doi: 10.1016/bs.podrm.2022.11.006, PMID 37061274.
4. Khan MS, Fatima M, Wahab S, Khalid M, Kesharwani P. Gallic acid loaded self-nanoemulsifying hydrogel-based drug delivery system against onychomycosis. Nanomedicine (Lond). 2024 Oct 20;19(25):2065-83. doi: 10.1080/17435889.2024.2386923, PMID 39143900.
5. Davidova S, Galabov AS, Satchanska G. Antibacterial antifungal antiviral activity and mechanisms of action of plant polyphenols. Microorganisms. 2024 Dec 4;12(12):2502. doi: 10.3390/microorganisms12122502, PMID 39770706.
6. Riaz Z, Baddi S, Gao F, Feng CL. Gallic acid-doped multifunctional hybrid hydrogel for antioxidant and antibacterial studies. Eur Polym J. 2024 Feb 21;206:112778. doi: 10.1016/j.eurpolymj.2024.112778.
7. Fan G, Xu Z, Liu X, Yin W, Sun L, Wu D. Antifungal efficacy of gallic acid extracted from pomegranate peel against Trichophyton rubrum: in vitro case study. Nat Prod Commun. 2023;18(1):1-6. doi: 10.1177/1934578X221148607.
8. Borgohain P, Saikia LR, Mahanta J. Herbal medicine as an alternative for the treatment of onychomycosis. Int J Bot Stud. 2022;7(2):29-34.
9. Brown A, Potesta M, Hameed A. Drug-induced liver injury secondary to terbinafine use. Cureus. 2024 Feb 19;16(2):e54453. doi: 10.7759/cureus.54453, PMID 38510874, PMCID PMC10952058.
10. Mohsin SA, Shaukat S, Nawaz M, Ur Rehman T, Irshad N, Majid M. Appraisal of selected ethnomedicinal plants as alternative therapies against onychomycosis: evaluation of synergy and time kill kinetics. Front Pharmacol. 2022 Nov 24;13:1067697. doi: 10.3389/fphar.2022.1067697, PMID 36506532.
11. Puri V, Froelich A, Shah P, Pringle S, Chen K, Michniak Kohn B. Quality by design guided development of polymeric nanospheres of terbinafine hydrochloride for topical treatment of onychomycosis using a nano-gel formulation. Pharmaceutics. 2022 Oct 12;14(10):2170. doi: 10.3390/pharmaceutics14102170, PMID 36297605.
12. Dehari D, Mehata AK, Priya V, Parbat D, Kumar D, Srivastava AK. Luliconazole nail lacquer for the treatment of onychomycosis: formulation characterization and in vitro and ex vivo evaluation. AAPS PharmSciTech. 2022 Jun 24;23(6):175. doi: 10.1208/s12249-022-02324-7, PMID 35750993.
13. Aldawsari MF, Alkholifi FK, Foudah AI, Alqarni MH, Alam A, Salkini MA. Gallic acid-loaded PLGA nanoparticles: a promising transdermal drug delivery system with antioxidant and antimicrobial agents. Pharmaceuticals (Basel). 2023 Aug 24;16(8):1090. doi: 10.3390/ph16081090, PMID 37631005.
14. Anjum A, Shabbir K, Din FU, Shafique S, Zaidi SS, Almari AH. Co-delivery of amphotericin B and pentamidine loaded niosomal gel for the treatment of cutaneous leishmaniasis. Drug Deliv. 2023 Dec 31;30(1):2173335. doi: 10.1080/10717544.2023.2173335, PMID 36722301.
15. Gugleva V, Ivanova N, Sotirova Y, Andonova V. Dermal drug delivery of phytochemicals with phenolic structure via lipid based nanotechnologies. Pharmaceuticals (Basel). 2021 Aug 24;14(9):837. doi: 10.3390/ph14090837, PMID 34577536.
16. Elshall AA, Ghoneim AM, Abdel Mageed HM, Osman R, Shaker DS. Ex vivo permeation parameters and skin deposition of melatonin-loaded microemulsion for treatment of alopecia. Futur J Pharm Sci. 2022 May 18;8(1):28. doi: 10.1186/s43094-022-00418-4.
17. Kasar PK, Kamble MA, Biyani KR, Kumbhar ST, Vidhate BV. Formulation and evaluation of topical gel of itraconazole. Int J Curr Pharm Res. 2018;10(1):32-5.
18. Manjubaashini N, Bargavi P, Balakumar S. Bioceramic and polycationic biopolymer nanocomposite scaffolds for improved wound self-healing and anti-inflammatory properties: an in vitro study. Biomater Sci. 2023;11(11):3921-37. doi: 10.1039/d3bm00169e, PMID 37092809.
19. Perissato BL, Dos Santos Pedroso R. Medicinal plants and onychomycosis: potential and evidence of antifungal activity an integrative review of the literature. J Med Plants Res. 2022 Jul 31;16(7):230-44. doi: 10.5897/JMPR2022.7239.
20. Javaid A, Sharma KK, Ka A, Verma A, Mudavath SL. Therapeutic potential of molsidomine loaded liquid crystal nanoparticles for the treatment and management of niacin-induced varicose veins: in vitro and in vivo studies. ACS Appl Bio Mater. 2024 Sep 24;7(11):7306-23. doi: 10.1021/acsabm.4c00980, PMID 39316777.
21. Ghannoum MA, Long L, Isham N, Bulgheroni A, Setaro M, Caserini M. Ability of hydroxypropyl chitosan nail lacquer to protect against dermatophyte nail infection. Antimicrob Agents Chemother. 2015 Apr;59(4):1844-8. doi: 10.1128/AAC.04842-14, PMID 25547349.
22. Temporiti ME, Guerini M, Baiguera RM, Buratti S, Desiderio A, Goppa L. Efficacy of bovine nail membranes as in vitro model for onychomycosis infected by trichophyton species. J Fungi (Basel). 2022 Oct 27;8(11):1133. doi: 10.3390/jof8111133, PMID 36354900.
23. Fluhr JW, Darlenski R, Surber CJ. Glycerol and the skin: holistic approach to its origin and functions. Br J Dermatol. 2008 Jul 1;159(1):23-34. doi: 10.1111/j.1365-2133.2008.08643.x, PMID 18510666.
24. Singh V, Verma R, Mittal V, Kaushik D. Preparation, evaluation and in vivo studies of novel herbal lipogel of Ocimum tenuiflorum (L.) extract for acne treatment. Int J App Pharm. 2025;17(4):127-44. doi: 10.22159/ijap.2025v17i4.53761.
25. Wunnoo S, Sermwittayawong D, Praparatana R, Voravuthikunchai SP, Jakkawanpitak C. Quercus infectoria gall ethanolic extract accelerates wound healing through attenuating inflammation and oxidative injuries in skin fibroblasts. Antioxidants (Basel). 2024 Sep 9;13(9):1094. doi: 10.3390/antiox13091094, PMID 39334753, PMCID PMC11428264.
26. Gil J, Solis M, Higa A, Davis SC. Candida albicans infections: a novel porcine wound model to evaluate treatment efficacy. BMC Microbiol. 2022;22(1):45. doi: 10.1186/s12866-022-02460-x, PMID 35120444.
Published
How to Cite
Issue
Section
Copyright (c) 2025 JANE GLENISHA LOBO, JOEL SYLVESTER SALDANHA, DIYA POLALI, JENITTA MARIA CARMEL, ASHWINI MADHAVA
This work is licensed under a Creative Commons Attribution 4.0 International License.
