In Vitro Antifungal Evaluation of a Berberine–Ellagic Acid Phytosome-Based Hydrogel Against Candida albicans

Candida albicans is an important fungal pathogen associated with superficial and opportunistic infections, creating a need for effective topical antifungal delivery systems. The present study aimed to evaluate the in vitro antifungal activity of an optimized berberine–ellagic acid (B+E) phytosome-based hydrogel against C. albicans. The optimized B+E phytosomes were incorporated into a Carbopol 940 and HPMC K15-based hydrogel matrix to develop a topical formulation. The antifungal activity was evaluated using the agar well diffusion method against C. albicans. The study included the pure B+E combination, optimized B+E phytosome hydrogel, ketoconazole as the standard antifungal drug, blank hydrogel, and normal control. Antifungal activity was assessed by measuring the zone of inhibition (ZOI). The optimized B+E phytosome hydrogel exhibited a ZOI of 23.54 mm, compared with 15.29 mm for the pure B+E combination and 26.64 mm for the standard antifungal drug. Thus, the phytosome-based hydrogel demonstrated an approximately 53.89% improvement in inhibition-zone diameter compared with pure B+E and achieved approximately 88.36% of the inhibition produced by the standard treatment. The optimized formulation also showed high drug content, with 95.86 ± 0.52% for berberine and 94.97 ± 0.61% for ellagic acid. The blank hydrogel and normal control showed no detectable inhibition. The enhanced activity may be attributed to improved dispersion and distribution of B+E within the phytosomal system and favorable diffusion characteristics of the hydrogel matrix. Overall, the findings demonstrate the potential of B+E phytosome-based hydrogel as a promising topical antifungal delivery system against C. albicans. Further in vivo and mechanistic studies are warranted.

1. 01.

   Talapko J, Juzbašić M, Matijević T, Pustijanac E, Bekić S, Kotris I, Škrlec I. Candida albicans-the virulence factors and clinical manifestations of infection. J. Fungi, 7, 1–19 (2021). doi: 10.3390/jof7020079.

   DOI: 10.3390/jof7020079 Google Scholar
2. 02.

   2. Zubovskaia A, Vazquez JA. The Upcoming Antifungal Drugs in Clinical Development for the Treatment of Invasive Candidiasis. Infect. Drug Resist., 19, (2026). doi: 10.2147/IDR.S547511.

   DOI: 10.2147/IDR.S547511 Google Scholar
3. 03.

   3. Purwaningsih I, Maksum IP, Sumiarsa D, Sriwidodo S. A Review of Fibraurea tinctoria and Its Component, Berberine, as an Antidiabetic and Antioxidant. Molecules, 28, (2023). doi: 10.3390/molecules28031294.

   DOI: 10.3390/molecules28031294 Google Scholar
4. 04.

   4. Susilawati S, Anwar C, Saleh I, Salni S. Flavonoid as Anti-Candida Agents. Indones. J. Fundam. Appl. Chem., 8, 88–97 (2023). doi: 10.24845/ijfac.v8.i2.88.

   DOI: 10.24845/ijfac.v8.i2.88 Google Scholar
5. 05.

   5. Sharifi-Rad J, Quispe C, Castillo CMS, Caroca R, Lazo-Vélez MA, Antonyak H, Polishchuk A, Lysiuk R, Oliinyk P, De Masi L, Bontempo P, Martorell M, Daştan SD, Rigano D, Wink M, Cho WC. Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential. Oxid. Med. Cell. Longev., 2022, (2022). doi: 10.1155/2022/3848084.

   DOI: 10.1155/2022/3848084 Google Scholar
6. 06.

   6. Othman B, Beigh S, Albanghali MA, Sindi AAA, Shanawaz MA, Ibahim MAEM, Marghani D, Kofiah Y, Iqbal N, Rashid H. Comprehensive pharmacokinetic profiling and molecular docking analysis of natural bioactive compounds targeting oncogenic biomarkers in breast cancer. Sci. Rep., 15, (2025). doi: 10.1038/s41598-024-84401-4.

   DOI: 10.1038/s41598-024-84401-4 Google Scholar
7. 07.

   7. Ghosh S, Solanki R, Bhatia D, Sankaranarayanan S. Nanomaterials for delivery of medicinal plant extracts and phytochemicals: Potential applications and future perspectives. Plant Nano Biol., 12, (2025). doi: 10.1016/j.plana.2025.100161.

   DOI: 10.1016/j.plana.2025.100161 Google Scholar
8. 08.

   8. Komal Maliwal*, Pankaj Chasta, Md. Zulphakar Ali. Review on Phytosomes: A Novel Drug Delivery System. Int. J. Pharm. Life Sci., 16, 1–5 (2025). doi: 10.64149/ijpls.16.5.1-5.

   DOI: 10.64149/ijpls.16.5.1-5 Google Scholar
9. 09.

   9. Sakure K, Patel A, Pradhan M, Badwaik HR. Recent Trends and Future Prospects of Phytosomes: A Concise Review. Indian J. Pharm. Sci., 86, (2024). doi: 10.36468/pharmaceutical-sciences.1334.

   DOI: 10.36468/pharmaceutical-sciences.1334 Google Scholar
10. 10.

    10. Talebi M, Shahbazi K, Dakkali MS, Akbari M, Almasi Ghale R, Hashemi S, Sashourpour M, Mojab F, Aminzadeh S. Phytosomes: A promising nanocarrier system for enhanced bioavailability and therapeutic efficacy of herbal products. Phytomedicine Plus, 5, (2025). doi: 10.1016/j.phyplu.2025.100779.

    DOI: 10.1016/j.phyplu.2025.100779 Google Scholar
11. 11.

    11. Pan P, Svirskis D, Waterhouse GIN, Wu Z. Hydroxypropyl Methylcellulose Bioadhesive Hydrogels for Topical Application and Sustained Drug Release: The Effect of Polyvinylpyrrolidone on the Physicomechanical Properties of Hydrogel. Pharmaceutics, 15, (2023). doi: 10.3390/pharmaceutics15092360.

    DOI: 10.3390/pharmaceutics15092360 Google Scholar
12. 12.

    12. Dahma Z, Álvarez-Álvarez C, de la Torre-Iglesias PM. A Mini-Review on Enhancing Solubility in Topical Hydrogel Formulations Using Solid Dispersion Technology for Poorly Water-Soluble Drugs. Colloids and Interfaces, 9, (2025). doi: 10.3390/colloids9020017.

    DOI: 10.3390/colloids9020017 Google Scholar
13. 13.

    13. Narvekar NG, Panda S, Jagtap VA. Development and physicochemical characterization of berberine–ellagic acid phytosomes incorporated into hydrogel for topical drug delivery. J. Chem. Lett., 7, 569–89 (2026). doi: 10.22034/jchemlett.2026.584392.1434.

    DOI: 10.22034/jchemlett.2026.584392.1434 Google Scholar
14. 14.

    14. Rafika R, Rahman R, Pratama R, Artati A, Mursalim M, Nasir M, Widarti W, Nuradi N, Nurdin N, Asyikin A, Nurisyah N, Abdullah T, Asmawati A. Rice Bran Dextrose Agar as a Cost-Effective Alternative to Standard Fungal Culture Media. Trop. J. Nat. Prod. Res., 9, 6209–13 (2025). doi: 10.26538/tjnpr/v9i12.39.

    DOI: 10.26538/tjnpr/v9i12.39 Google Scholar
15. 15.

    15. Khudhair AS, Abdalkarim Sabri L. Preparation and evaluation of topical hydrogel containing ketoconazole-loaded bilosomes. Acta Pharm. Sci., 62, 762–77 (2024). doi: 10.23893/1307-2080.aps6250.

    DOI: 10.23893/1307-2080.aps6250 Google Scholar
16. 16.

    16. Bicer M, Öztürk E, Sener F, Hakki SS, Fidan Ö. Antifungal Efficacy of 3D-Cultured Palatal Mesenchymal Stem Cells and Their Secreted Factors against Candida albicans. ACS Infect. Dis., 11, 2894–906 (2025). doi: 10.1021/acsinfecdis.5c00657.

    DOI: 10.1021/acsinfecdis.5c00657 Google Scholar
17. 17.

    17. Safanda Tiara Fitri, Maulidiyah Cholifah, Isna Wulan Mukarromah, Renny Angreyni, Ferdiana Putri Gita Veronika, Dewi Rahmawati, Dzakiya Zhihrotulwida, M. Fithrul Mubarak. Artikel Review : Evaluasi pada Sediaan Steril. An-Najat, 3, 70–81 (2025). doi: 10.59841/an-najat.v3i1.2279.

    DOI: 10.59841/an-najat.v3i1.2279 Google Scholar
18. 18.

    18. Shaaban S, Hamad GM, Genena S, Meheissen MA, Moussa S. Evaluation of the antibacterial activity of Lactobacilli probiotics supernatants against Enterococcus faecalis (in-vitro study). BMC Oral Health, 22, (2022). doi: 10.1186/s12903-022-02434-5.

    DOI: 10.1186/s12903-022-02434-5 Google Scholar