Emerging Trends in Antifungal Treatment: Role of Gels, Natural Products, and Innovative Targets

Authors

  • Ayush Kalhansh Himalayan Institute of Pharmacy Kala-Amb, Distt-Sirmour, Himachal Pradesh, India-173030
  • Sakshi Tomar Himalayan Institute of Pharmacy Kala-Amb, Distt-Sirmour, Himachal Pradesh, India-173030
  • Ram Babu Sharma Himalayan Institute of Pharmacy Kala-Amb, Distt-Sirmour, Himachal Pradesh, India-173030

Abstract

Growing medication resistance limits the efficacy of traditional antifungal treatments, making fungal infections a major worldwide health problem, especially among immunocompromised people. This review focuses on new molecular targets, gel-based drug delivery methods, and drugs derived from natural products as developing trends in antifungal therapy. Due to their biocompatibility, capacity to improve drug stability, and enhanced patient compliance, gels have drawn interest as topical delivery systems that provide localised therapy with less systemic side effects. Natural products, such as marine chemicals, plant-derived metabolites, and microbial bio actives, are highlighted as a possible source of novel antifungal medicines with a variety of actions, including enzyme inhibition and membrane disruption. In order to address the present problems with resistance, novel therapeutic targets are being investigated, including fungal cell wall production, biofilm formation, hyphal morphogenesis, mitochondrial function, and heat shock proteins. Optimising treatment approaches is further aided by developments in pharmacokinetics and pharmacodynamics, as well as better diagnostic instruments and antifungal stewardship. All things considered, combining innovative drug delivery strategies with targeted treatments and natural substances presents a potential path toward the creation of safer and more potent antifungal treatments.

Keywords:   Antifungal therapy, Antifungal resistance Gel-based drug delivery, Natural products, Fungal biofilms, Novel molecular targets, Topical drug delivery, Drug repurposing

Keywords:

Antifungal therapy, Antifungal resistance Gel-based drug delivery, Natural products, Novel molecular targets, Topical drug delivery, Drug repurposing

DOI

https://doi.org/10.22270/jddt.v16i10.8065

Author Biographies

Ayush Kalhansh, Himalayan Institute of Pharmacy Kala-Amb, Distt-Sirmour, Himachal Pradesh, India-173030

Himalayan Institute of Pharmacy Kala-Amb, Distt-Sirmour, Himachal Pradesh, India-173030

Sakshi Tomar , Himalayan Institute of Pharmacy Kala-Amb, Distt-Sirmour, Himachal Pradesh, India-173030

Himalayan Institute of Pharmacy Kala-Amb, Distt-Sirmour, Himachal Pradesh, India-173030

Ram Babu Sharma, Himalayan Institute of Pharmacy Kala-Amb, Distt-Sirmour, Himachal Pradesh, India-173030

Himalayan Institute of Pharmacy Kala-Amb, Distt-Sirmour, Himachal Pradesh, India-173030

References

1. Metta S, Amir KM, Lakshmi MS, Devi P, Shruthi K, A review: pharmaceutical gels and its types with prominence role of its drug delivery systems, International Journal of Research and Analytical Reviews,2023;10 (2):686-691.

2. Paye M, Barel AO, Maibach HI. Handbook of cosmetic science and technology. 2nd ed. New York: Taylor & Francis; 2006. https://doi.org/10.1201/b14400 PMCid:PMC538828

3. Godge GR, Bharat SC, Shaikh AB, Randhawan BB, Raskar MA, Hiremath SN. Formulation perspectives in topical antifungal drug therapy, a review, Journal of Drug Delivery and Therapeutics, 2023;13(5):110-119. https://doi.org/10.22270/jddt.v13i5.6079

4. Rajasekaran A, Govindarjan A, Ramasamy A, Formulation and evaluation of topical herbal gel for the treatment of arthritis in animal model, Brazilian Journal of Pharmaceutical Sciences, 2016;52(3):493-507. https://doi.org/10.1590/s1984-82502016000300015

5. Garje KL, Salunkhe KS, Review on: anti-inflammatory herbal gel of Boswellia serrata & Vitex negundo, International Journal of Pharmacy and Biological Sciences, 2013;3(2):374-382.

6. Groll AH, Shah PM, Mentzel C, Schneider M, Just-Nuebling G, Huebner K, Trends in the postmortem epidemiology of invasive fungal infections at a university hospital, Journal of Infection ,1996;33(1):23-32. https://doi.org/10.1016/S0163-4453(96)92700-0 PMid:8842991

7. Denning DW, Evans EG, Kibbler CC, Richardson MD, Roberts MM, Rogers TR, Guidelines for the investigation of invasive fungal infections in haematological malignancy and solid organ transplantation, British Society for Medical Mycology, European Journal of Clinical Microbiology & Infectious Diseases, 1997;16(6):424-436. https://doi.org/10.1007/BF02471906 PMid:9248745

8. Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC, Hidden killers: human fungal infections, Science Translational Medicine, 2012; 4(165):165rv13. https://doi.org/10.1126/scitranslmed.3004404 PMCid:PMC3627207

9. Fidel PL Jr, Barousse M, Espinosa T, Ficarra M, Sturtevant J, Martin DH, An intravaginal live Candida challenge in humans leads to new hypotheses for the immune pathogenesis of vulvovaginal candidiasis, Infection and Immunity, 2004; 72 (5):2939-2946. https://doi.org/10.1128/IAI.72.5.2939-2946.2004 PMid:15102806 PMCid:PMC387876

10. Byrnes EJ 3rd, Li W, Lewit Y, Ma H, Voelz K, Ren P, Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States, Public Library of Science Pathogens, 2010;6(4):e1000850 https://doi.org/10.1371/journal.ppat.1000850 PMid:20421942

11. Talaviya S, Majmudar F, Recent developments in antifungal agents. International Journal of Pharmacy and Pharmaceutical Sciences, 2012;4(Suppl 4):4-10.

12. Sathyan G, Ritschel WA, Hussain AS, Transdermal delivery of tacrine ;Identification of a suitable delivery vehicle, International Journal of Pharmaceutics, 1995;114 (1):75-83. https://doi.org/10.1016/0378-5173(94)00214-P

13. Gungor S, Erdal MS, Aksu B, New formulation strategies in topical antifungal therapy. Journal of Cosmetics, Dermatological Sciences and Applications, 2013;3: 56-65. https://doi.org/10.4236/jcdsa.2013.31A009

14. Chen SC, Sorrell TC, Antifungal agents, Medical Journal of Australia, 2007; 187 (7):404-409. https://doi.org/10.5694/j.1326-5377.2007.tb01313.x PMid:17908006

15. Boddy L, Interactions with humans and other animals. In: Watkinson SC, Boddy L, Money NP, editors. The fungi. 3rd ed. Amsterdam: Academic Press; 2016. p. 293- 336. https://doi.org/10.1016/B978-0-12-382034-1.00009-8

16. Natarajan V, Nath AK, Thappa DM, Singh R, Verma SK, Coexistence of onychomycosis in psoriatic nails: a descriptive study, Indian Journal of Dermatology, Venereology and Leprology, 2010;76 (6):723. https://doi.org/10.4103/0378-6323.72468 PMid:21079333

17. Ajello LA, taxonomic review of the dermatophytes and related species. Sabouraudia, 1968; 6(2):147-159. https://doi.org/10.1080/00362176885190271 PMid:4869482

18. Sulaiman IM, Jacobs E, Simpson S, Kerdahi K, Genetic characterization of fungi isolated from the environmental swabs collected from a compounding center known to cause multistate meningitis outbreak in United States using ITS sequencing, Pathogens. 2014; 3(3):732-742. https://doi.org/10.3390/pathogens3030732 PMid:25438021 PMCid:PMC4243438

19. Robbins N, Wright GD, Cowen LE, Antifungal drugs: the current armamentarium and development of new agents, Microbiology Spectrum, 2016; 4 (5):903-922. https://doi.org/10.1128/microbiolspec.FUNK-0002-2016 PMid:27763259

20. Steimbach LM, Tonin FS, Virtuoso S, Borba HH, Sanches AC, Wiens A, Efficacy and safety of amphotericin B lipid-based formulations-a systematic review and meta-analysis, mycosis, 2017;60(3):146-154. https://doi.org/10.1111/myc.12585 PMid:27878878

21. Balcerek MI, Stewart AG, Chapman P, Lazarus S, Reducing the off-target endocrinologic adverse effects of azole antifungals-can it be done? International Journal of Antimicrobial Agents, 2022; 59(5):106587. https://doi.org/10.1016/j.ijantimicag.2022.106587 PMid:35405267

22. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky- Zeichner L, Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America, Clinical Infectious Diseases, 2016;62(4):e1-e50. https://doi.org/10.1093/cid/civ933 PMid:26679628 PMCid:PMC4725385

23. Vermes A, Guchelaar HJ, Dankert J, Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions, Journal of Antimicrobial Chemotherapy, 2000;46(2):171-179. https://doi.org/10.1093/jac/46.2.171 PMid:10933638

24. Haghani I, Babaie M, Hoseinnejad A, Rezaei-Matehkolaei A, Mofarrah R, Yahyazadeh Z, High prevalence of terbinafine resistance among Trichophyton mentagrophytes/T. interdigitale species complex, a cross-sectional study from 2021 to 2022 in northern parts of Iran, Mycopathologia, 2024;189 (4):52-59. https://doi.org/10.1007/s11046-024-00855-0 PMid:38864945

25. Lepak AJ, Andes DR, Antifungal pharmacokinetics and pharmacodynamics, Cold Spring Harbor perspectives in medicine. 2015;5(5):a019653. https://doi.org/10.1101/cshperspect.a019653 PMid:25384765 PMCid:PMC4448584

26. Lewis RE, Current concepts in antifungal pharmacology, Mayo Clinic Proceedings, 2011; 86(8):805-817. https://doi.org/10.4065/mcp.2011.0247 PMid:21803962 PMCid:PMC3146381

27. Bellmann R, Smuszkiewicz P, Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients, Infection. 2017; 45(6):737-779. https://doi.org/10.1007/s15010-017-1042-z PMid:28702763 PMCid:PMC5696449

28. Balkis MM, Leidich SD, Mukherjee PK, Ghannoum MA, Mechanisms of fungal resistance: an overview. Drugs, 2002; 62 (7):1025-1040. https://doi.org/10.2165/00003495-200262070-00004 PMid:11985489

29. De Francesco M, Drug-resistant Aspergillus spp.: a literature review of its resistance mechanisms and its prevalence in Europe, Pathogens, 2023;12 (10):1305-1312. https://doi.org/10.3390/pathogens12111305 PMid:38003770 PMCid:PMC10674884

30. Szymański M, Chmielewska S, Czyżewska U, Malinowska M, Tylicki A, Echinocandins-structure, mechanism of action and use in antifungal therapy, Journal of Enzyme Inhibition and Medicinal Chemistry, 2022;37 (1):876-894. https://doi.org/10.1080/14756366.2022.2050224 PMid:35296203 PMCid:PMC8933026

31. Gupta AK, Wang T, Mann A, Piguet V, Chowdhary A, Bakotic WL, Mechanisms of resistance against allylamine and azole antifungals in Trichophyton: A renewed call for innovative molecular diagnostics in susceptibility testing, Public Library of Science pathogens, 2025;21 (2):e1012913. https://doi.org/10.1371/journal.ppat.1012913 PMid:39932950 PMCid:PMC11813129

32. Pemán J, Cantón E, Espinel-Ingroff A, Antifungal drug resistance mechanisms, Expert Review of Anti-Infective Therapy, 2009; 7(4):453-460. https://doi.org/10.1586/eri.09.18 PMid:19400764

33. Fang W, Wu J, Cheng M, Zhu X, Du M, Chen C, Diagnosis of invasive fungal infections: challenges and recent developments, Journal of Biomedical Science2023;30:42-47. https://doi.org/10.1186/s12929-023-00926-2 PMid:37337179 PMCid:PMC10278348

34. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016; 62(4): e1-50. https://doi.org/10.1093/cid/civ933 PMid:26679628 PMCid:PMC4725385

35. Fung S, Shirley M. Rezafungin: a review in invasive candidiasis. Drugs. 2025; 85: 415-423. https://doi.org/10.1007/s40265-024-02134-0 PMid:39913021

36. Ghannoum M, Arendrup MC, Chaturvedi VP, Lockhart SR, McCormick TS, Chaturvedi S, Ibrexafungerp: a novel oral triterpenoid antifungal in development for the treatment of Candida auris infections, Antibiotics (Basel). 2020;9(9):539-545. https://doi.org/10.3390/antibiotics9090539 PMid:32854252 PMCid:PMC7559578

37. Vazquez JA, Pappas PG, Boffard K, Paruk F, Bien PA, Tawadrous M, Clinical efficacy and safety of a novel antifungal, fosmanogepix, in patients with candidemia caused by Candida auris: results from a phase 2 trial, Antimicrobial Agents and Chemotherapy, 2023;67(5): e0141922. https://doi.org/10.1128/aac.01419-22 PMid:37022196 PMCid:PMC10190264

38. Karthaus M, Guideline based treatment of invasive aspergillosis. Mycoses. 2010; 53 Suppl 1:36-43. https://doi.org/10.1111/j.1439-0507.2009.01840.x PMid:20433655

39. Douglas AP, Smibert OC, Bajel A, Halliday CL, Lavee O, McMullan B, Consensus guidelines for the diagnosis and management of invasive aspergillosis, Internal Medicine Journal, 2021; 51 (2):143-176. https://doi.org/10.1111/imj.15591 PMid:34937136

40. Brunet K, Rammaert B, Mucormycosis treatment: recommendations, latest advances, and perspectives, Journal de Mycologie Médicale, 2020; 30(3):101007. https://doi.org/10.1016/j.mycmed.2020.101007 PMid:32718789

41. Jarvis JN, Lawrence DS, Meya DB, Kagimu E, Kasibante J, Mpoza E, Single-dose liposomal amphotericin B treatment for cryptococcal meningitis, The New England Journal of Medicine, 2022;386(12):1109-1120. https://doi.org/10.1056/NEJMoa2111904 PMid:35320642

42. Yoshida M. Development of a method of measuring β-D-glucan and its use in preemptive therapy for invasive fungal infections, International Journal of Molecular Sciences, 2021;22(17):9265. https://doi.org/10.3390/ijms22179265 PMid:34502174 PMCid:PMC8431658

43. Wiederhold NP, Antifungal susceptibility testing: a primer for clinicians, Open Forum Infectious Diseases. 2021; 8(11): ofab444. https://doi.org/10.1093/ofid/ofab444 PMid:34778489

44. Chakrabarti A, Mohamed N, Capparella MR, Townsend A, Sung AH, Yura R, The role of diagnostics-driven antifungal stewardship in the management of invasive fungal infections: a systematic literature review, Open Forum Infectious Diseases,2022; 9(7): ofac234 https://doi.org/10.1093/ofid/ofac234 PMid:35873300 PMCid:PMC9297315

45. Procacci C, Marras L, Maurmo L, Vivanet G, Scalone L, Bertolino G, Antifungal stewardship in invasive fungal infections, a systematic review, Advances in Experimental Medicine and Biology, 2025;1476: 49-68. https://doi.org/10.1007/5584_2024_798 PMid:38337088

46. Costa Vasconcelos Alves AM, Cruz-Martins N, Rodrigues CF, Marine compounds with anti-Candida sp. activity: a promised "land" for new antifungals, Journal of Fungi,2022; 8(7):1-10. https://doi.org/10.3390/jof8070669 PMid:35887426 PMCid:PMC9320905

47. Bharathi D, Lee J, Recent advances in marine-derived compounds as potent antibacterial and antifungal agents: a comprehensive review, Marine Drugs, 2024;22(8):1-22. https://doi.org/10.3390/md22080348 PMid:39195465 PMCid:PMC11355281

48. Hang S, Lu H, Jiang Y. Marine-derived metabolites act as promising antifungal agents. Marine Drugs, 2024;22(4):1-28. https://doi.org/10.3390/md22040180 PMid:38667797 PMCid:PMC11051449

49. Kubota T, Nakamura K, Kurimoto SI, Sakai K, Fromont J, Gonoi T, Zamamidine D, a manzamine alkaloid from an Okinawan Amphimedon sp. marine sponge, Journal of Natural Products2017;80(4):1196-1199. https://doi.org/10.1021/acs.jnatprod.6b01110 PMid:28207259

50. Youssef DTA, Shaala LA, Mohamed GA, Badr JM, Bamanie FH, Ibrahim SRM, Theonellamide G, a potent antifungal and cytotoxic bicyclic glycopeptide from the Red Sea marine sponge Theonella swinhoei, Marine Drugs,2014;12(4):1911-1923. https://doi.org/10.3390/md12041911 PMid:24694570 PMCid:PMC4012434

51. Fan H, Shi ZM, Lei YH, Si-Tu MX, Zhou FG, Feng C, Rare carbon-bridged citrinin dimers from the starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2, Marine Drugs, 2022;20(7):1-15. https://doi.org/10.3390/md20070443 PMid:35877736 PMCid:PMC9317178

52. Xu T, Feng Q, Jacob MR, Avula B, Mask MM, Baerson SR, The marine sponge-derived polyketide endoperoxide plakortide F acid mediates its antifungal activity by interfering with calcium homeostasis, Antimicrobial Agents and Chemotherapy, 2011; 55 (4):1611-1621. https://doi.org/10.1128/AAC.01022-10 PMid:21300833 PMCid:PMC3067192

53. Chiba H, Agematu H, Dobashi K, Yoshioka T, Rhodopeptins, novel cyclic tetrapeptides with antifungal activities from Rhodococcus sp. II. Structure elucidation, The Journal of Antibiotics, 1999; 52(8):700-709. https://doi.org/10.7164/antibiotics.52.700 PMid:10580383

54. Gao J, Hamann MT, Chemistry and biology of kahalalides, Chemical Society Reviews, 2011; 111(5):3208-3235. https://doi.org/10.1021/cr100187n PMid:21480581 PMCid:PMC4895206

55. Yibmantasiri P, Leahy DC, Busby BP, Angermayr SA, Sorgo AG, Boeger K, Molecular basis for fungicidal action of neothyonidioside, a triterpene glycoside from the sea cucumber, Australostichopus mollis, Molecular Bio Systems, 2012;8(3):902-912. https://doi.org/10.1039/C2MB05426D PMid:22271309

56. Razmi M, Kim J, Chinnici J, Busarajan S, Vuppalapaty H, Lankipalli D, Candida albicans mannosidases, Dfg5 and Dcw1, are required for cell wall integrity and pathogenesis, Journal of Fungi, 2024;10 (8):525-532. https://doi.org/10.3390/jof10080525 PMid:39194851 PMCid:PMC11355814

57. Draelos M, Yokoyama K. Biosynthesis and mechanism of action of antifungal peptidyl nucleoside natural products. In: Liu H, Tadhg P, editors. Comprehensive natural products III. Amsterdam: Elsevier; 2020:613-641. https://doi.org/10.1016/B978-0-12-409547-2.14680-3

58. Hector RF, Zimmer BL, Pappagianis D, and Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis, Antimicrobial Agents and Chemotherapy, 1990; 34(4):587-593. https://doi.org/10.1128/AAC.34.4.587 PMid:2344165 PMCid:PMC171648

59. Cheung YY, Hui M, Effects of echinocandins in combination with nikkomycin Z against invasive Candida albicans bloodstream isolates and the fks mutants, Antimicrobial Agents and Chemotherapy ,2017;61(11):1-4. https://doi.org/10.1128/AAC.00619-17 PMid:28827418 PMCid:PMC5655089

60. Chiou CC, Mavrogiorgos N, Tillem E, Hector R, Walsh TJ. Synergy, pharmacodynamics, and time-sequenced ultrastructural changes of the interaction between nikkomycin Z and the echinocandin FK463 against Aspergillus fumigatus, Antimicrobial Agents and Chemotherapy, 2001;45(12):3310-3321. https://doi.org/10.1128/AAC.45.12.3310-3321.2001 PMid:11709302 PMCid:PMC90831

61. Hector RF, Compounds active against cell walls of medically important fungi. Clinical Microbiology Reviews, 1993; 6(1):1-21. https://doi.org/10.1128/CMR.6.1.1 PMid:8457977 PMCid:PMC358263

62. Pierce CG, Chaturvedi AK, Lazzell AL, Powell AT, Saville SP, McHardy SF, A novel small molecule inhibitor of Candida albicans biofilm formation, filamentation and virulence with low potential for the development of resistance, Nature Partner Journal,2015;1:15012. https://doi.org/10.1038/npjbiofilms.2015.12 PMid:26691764 PMCid:PMC4681527

63. Romo JA, Pierce CG, Chaturvedi AK, Lazzell AL, McHardy SF, Saville SP, Development of antivirulence approaches for candidiasis via a novel series of small-molecule inhibitors of Candida albicans filamentation, mBio. 2017;8(6): e01991-17. https://doi.org/10.1128/mBio.01991-17 PMid:29208749 PMCid:PMC5717394

64. Zhang T, Chen W, The Candida albicans inhibitory activity of the extract from papaya (Carica papaya L.) seed relates to mitochondria dysfunction, International Journal of Molecular Sciences,2017;18(9):1-18. https://doi.org/10.3390/ijms18091858 PMid:28841152 PMCid:PMC5618507

65. Hareyama Y, Tarao M, Toyota K, Furukawa T, Fujii Y, Kushiro M, Effects of four isothiocyanates in dissolved and gaseous states on the growth and aflatoxin production of Aspergillus flavus in vitro, Toxins (Basel). 2022; 14(11):756-764. https://doi.org/10.3390/toxins14110756 PMid:36356006 PMCid:PMC9697429

66. Yi W, Gu L, Wang Y, Lin J, Zhang L, Wang Q, Diao W, Qi Y, Chi M, Yin M, Benzyl isothiocyanate improves the prognosis of Aspergillus fumigatus keratitis by reducing fungal load and inhibiting Mincle signal pathway, Frontiers in Microbiology,2023;14: 1119568. https://doi.org/10.3389/fmicb.2023.1119568 PMid:36876115 PMCid:PMC9978348

67. Robbins N, Uppuluri P, Nett J, Rajendran R, Ramage G, Lopez-Ribot JL, Hsp90 governs dispersion and drug resistance of fungal biofilms, Public Library of Science Pathogens, 2011; 7(9): e1002257. https://doi.org/10.1371/journal.ppat.1002257 PMid:21931556 PMCid:PMC3169563

68. Yuan R, Tu J, Sheng C, Chen X, Liu N, Effects of Hsp90 inhibitor ganetespib on inhibition of azole-resistant Candida albicans, Frontiers in Microbiology, 2021;12: 680382. https://doi.org/10.3389/fmicb.2021.680382 PMid:34093502

Published

2026-10-15
Statistics
Abstract Display: 0
PDF Downloads: 0
PDF Downloads: 0

How to Cite

1.
Kalhansh A, Tomar S, Sharma RB. Emerging Trends in Antifungal Treatment: Role of Gels, Natural Products, and Innovative Targets. J. Drug Delivery Ther. [Internet]. 2026 Oct. 15 [cited 2026 Oct. 15];16(10):209-1. Available from: https://www.jddtonline.info/index.php/jddt/article/view/8065

How to Cite

1.
Kalhansh A, Tomar S, Sharma RB. Emerging Trends in Antifungal Treatment: Role of Gels, Natural Products, and Innovative Targets. J. Drug Delivery Ther. [Internet]. 2026 Oct. 15 [cited 2026 Oct. 15];16(10):209-1. Available from: https://www.jddtonline.info/index.php/jddt/article/view/8065