International Journal of Drug Delivery Technology
Volume 15, Issue 2

Enhanced Antifungal Efficacy of Clove Oil using Nanosponges: A Novel Topical Delivery System 

Anuradha Salunkhe, Smita More, Shashikant Dhole

Department of Pharmaceutics, PES Modern College of Pharmacy (for Ladies), Moshi, Affiliated to Savitribai Phule Pune University, Pune, Maharashtra, India

Received: 21st Jan, 2025; Revised: 14th Mar, 2025; Accepted: 19th May, 2025; Available Online: 25th Jun, 2025

ABSTRACT

Clove oil (CO), derived from Syzygium aromaticum, is recognized for its broad-spectrum antimicrobial, antifungal, and anti-inflammatory properties. Still, its pharmaceutical uses are narrow due to poor aqueous solubility, chemical instability and potential skin irritation. This study aimed to enhance CO’s therapeutic efficacy using nanosponges as a novel delivery system. A 3² complete factorial design was used to optimise the synthesis of ethyl cellulose nanosponges, which were achieved utilising the emulsion solvent diffusion method. optimized formulation (F4) exhibited high entrapment efficiency (94.38%) and practical yield (93.23%). The nanosponge-loaded gel exhibited excellent physicochemical properties, including a pH of 5.4, viscosity of 13,092 cps, and sustained drug release (92.3% over 12 hours) following zero-order kinetics. In vivo studies in an immunosuppressed rat model of Candida albicans infection exhibited significantly improved antifungal efficacy with the nanosponges-loaded CO gel compared to pure CO gel. Histopathological analysis confirmed enhanced skin recovery, while the Draize patch test indicated no skin irritation. Stability studies further validated the formulation’s long-term integrity, with consistent drug release over 90 days. The results suggest that nanosponges-based CO delivery enhances antifungal activity, improves bioavailability, and minimizes skin irritation, making it a promising approach for topical antifungal therapy.

Keywords: Clove oil, Nanosponges, Antifungal therapy, Topical drug delivery, Candida albicans, Sustained release

How to cite this article: Anuradha Salunkhe, Smita More, Shashikant Dhole. Enhanced Antifungal Efficacy of Clove Oil using Nanosponges: A Novel Topical Delivery System. International Journal of Drug Delivery Technology. 2025;15(2):545-57. doi: 10.25258/ijddt.15.2.23

REFERENCES

  1. Prashar A, Locke IC, Evans CS. Cytotoxicity of clove (Syzygium aromaticum) oil and its major components to human skin cells. Cell Proliferation. 2006 Aug;39(4):241-8.
  2. Chaieb K, Hajlaoui H, Zmantar T, Kahla‐Nakbi AB, Rouabhia M, Mahdouani K, Bakhrouf A. The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzygium aromaticum Myrtaceae): a short review. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2007 Jun;21(6):501-6.
  3. Burt S. Essential oils: their antibacterial properties and potential applications in foods—a review. International journal of food microbiology. 2004 Aug 1;94(3):223-53.
  4. Pinto E, Vale-Silva L, Cavaleiro C, Salgueiro L. Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species. Journal of medical microbiology. 2009 Nov;58(11):1454-62.
  5. Kamatou GP, Vermaak I, Viljoen AM. Eugenol—from the remote Maluku Islands to the international market place: a review of a remarkable and versatile molecule. Molecules. 2012 Jun 6;17(6):6953-81.
  6. Bhuiyan MN, Begum J, Nandi NC, Akter F. Constituents of the essential oil from leaves and buds of clove (Syzigium caryophyllatum (L.) Alston). African Journal of Plant Science. 2010 Nov;4(11):451-4.
  7. Ali BM, Ibrahim O. Antifungal activity of clove (Syzygium aromaticum) essential oil extract against induced topical skin infection by Candida albicans in mice in vivo. The Egyptian Journal of Hospital Medicine. 2023 Apr 1;91(1):3855-61.
  8. Turek C, Stintzing FC. Stability of essential oils: a review. Comprehensive reviews in food science and food safety. 2013 Jan;12(1):40-53.
  9. Chattar H, Pimple B, Kuchekar M, Tare H, Wagh V, Kachave R. Comparative antifungal potential of six formulated herbal shampoos against Candida albicans causing Seborrheic dermatitis. Microbial Biosystems. 2024 Jun 1;9(1):17-26.
  10. Cavalli R, Trotta F, Tumiatti W. Cyclodextrin-based nanosponges for drug delivery. Journal of inclusion phenomena and macrocyclic chemistry. 2006 Oct;56:209-13.
  11. Trotta F, Zanetti M, Cavalli R. Cyclodextrin-based nanosponges as drug carriers. Beilstein journal of organic chemistry. 2012 Nov 29;8(1):2091-9.
  12. Singh R, Lillard Jr JW. Nanoparticle-based targeted drug delivery. Experimental and molecular pathology. 2009 Jun 1;86(3):215-23.
  13. Singh AR, Desu PK, Nakkala RK, Kondi V, Devi S, Alam MS, Hamid H, Athawale RB, Kesharwani P. Nanotechnology-based approaches applied to nutraceuticals. Drug delivery and translational research. 2022 Mar 1:1-5.
  14. Biju P, Shenoy MM, Tellis R, Bhat R, Das R, Prabhu A, Ahmed MG, Ghate V. Novel Ketoconazole-Loaded Niosomal Gel with Carbamide for Enhanced Topical Delivery and Skin Hydration in Fungal Infections. Journal of Pharmaceutical Innovation. 2025 Apr;20(2):1-8.
  15. Ahmed MM, Fatima F, Anwer MK, Ibnouf EO, Kalam MA, Alshamsan A, Aldawsari MF, Alalaiwe A, Ansari MJ. Formulation and in vitro evaluation of topical nanosponge-based gel containing butenafine for the treatment of fungal skin infection. Saudi Pharmaceutical Journal. 2021 May 1;29(5):467-77.
  16. Mustafa G, Almohsen RA, Alotaibi MM, Alotaibi MM, Alotaibi RM, El Kirdasy AF, Khan FR, Alharthi NS, Binshaya AS, Alotaibi F, Ansari MS. Characterization and optimization of clove oil-loaded nanomicelles for the possible topical use of bacterial infection-led atopic dermatitis. Beni-Suef University Journal of Basic and Applied Sciences. 2023 Oct 16;12(1):91.
  17. Bouzabata A, Bazzali O, Cabral C, Gonçalves MJ, Cruz MT, Bighelli A, Cavaleiro C, Casanova J, Salgueiro L, Tomi F. New compounds, chemical composition, antifungal activity and cytotoxicity of the essential oil from Myrtus nivellei Batt. & Trab., an endemic species of Central Sahara. Journal of ethnopharmacology. 2013 Oct 7;149(3):613-20.
  18. Garg A, Lai WC, Chopra H, Agrawal R, Singh T, Chaudhary R, Dubey BN. Nanosponge: A promising and intriguing strategy in medical and pharmaceutical Science. Heliyon. 2024 Jan 15;10(1).
  19. Penjuri SC, Ravouru N, Damineni S, Bns S, Poreddy SR. Formulation and evaluation of lansoprazole loaded Nanosponges. Turk J Pharm Sci. 2016 Sep 1;13(3):304-10.
  20. Kaur M, Nagpal M, Singh M, Singh TG, Aggarwal G, Dhingra GA. Improved antibacterial activity of topical gel-based on nanosponge carrier of cinnamon oil. BioImpacts: BI. 2020 Mar 24;11(1):23.
  21. Ghurghure SM, Ka K, Ys T, Ma P. Preparation and in-vitro evaluation of Itraconazole loaded nanosponges for topical drug delivery. Indo Am. J. Pharm. Res. 2019;9:1999-2013.
  22. Saran S, Menon S, Shailajan S, Pokharna P. Validated RP-HPLC method to estimate eugenol from commercial formulations like Caturjata Churna, Lavangadi Vati, Jatiphaladi Churna, Sitopaladi Churna and clove oil. Journal of pharmacy research. 2013 Jan 1;6(1):53-60.
  23. Kirankumar A, Ganeshkumar Y. Design and characterization of nano sponges loaded vaginal gels of Voriconazole. Brazilian Journal of Development. 2024 Jan 5;10(1):379-401.
  24. Abbas N, Irfan M, Hussain A, Arshad MS, Hussain SZ, Latif S, Bukhari NI. Development and evaluation of scaffold-based nanosponge formulation for controlled drug delivery of naproxen and ibuprofen. Tropical Journal of Pharmaceutical Research. 2018 Oct 5;17(8):1465-74.
  25. Mitrović D, Zaklan D, Đanić M, Stanimirov B, Stankov K, Al-Salami H, Pavlović N. The Pharmaceutical and Pharmacological Potential Applications of Bilosomes as Nanocarriers for Drug Delivery. Molecules. 2025 Mar 6;30(5):1181.
  26. Borse VA, Gangude AB, Deore AB. Formulation and evaluation of antibacterial topical gel of doxycycline hyclate, neem oil and tea tree oil. Indian J. Pharm. Educ. Res. 2020 Jan 1;54(10):206-12.
  27. Parhi R, Terapalli BR, Teja BB. Formulation and in vitro evaluation of minoxidil topical gel. Turk J Pharm Sci. 2014 Jul 1;11(2):153-62.
  28. Bhise SB, Dias RJ, Dhavale SG, Mali KK. Laboratory manual of biopharmaceutics and pharmacokinetics. Trinity Publishing House, India. 2010;1:1-66.
  29. Ghose A, Nabi B, Rehman S, Md S, Alhakamy NA, Ahmad OA, Baboota S, Ali J. Development and evaluation of polymeric nanosponge hydrogel for terbinafine hydrochloride: Statistical optimization, in vitro and in vivo Polymers. 2020 Dec 3;12(12):2903.
  30. Asghar Z, Jamshaid T, Jamshaid U, Madni A, Akhtar N, Lashkar MO, Gad HA. In vivo evaluation of miconazole-nitrate-loaded transethosomal gel using a rat model infected with Candida albicans. Pharmaceuticals. 2024 Apr 24;17(5):546.
  31. Sivadasan D, Venkatesan K, Mohamed JM, Alqahtani S, Asiri YI, Faisal MM, Ibrahim AE, Alrashdi YB, Menaa F, Deeb SE. Application of 32 factorial design for loratadine-loaded nanosponge in topical gel formulation: comprehensive in-vitro and ex vivo evaluations. Scientific Reports. 2024 Mar 16;14(1):6361.
  32. Biernasiuk A, Baj T, Malm A. Clove essential oil and its main constituent, eugenol, as potential natural antifungals against Candida spp. alone or in combination with other antimycotics due to synergistic interactions. Molecules. 2022 Dec 26;28(1):215.
  33. Ahmed MM, Fatima F, Anwer MK, Ansari MJ, Das SS, Alshahrani SM. Development and characterization of ethyl cellulose nanosponges for sustained release of brigatinib for the treatment of non-small cell lung cancer. Journal of Polymer Engineering. 2020 Nov 26;40(10):823-32.
  34. Aman RM, Abu Hashim II, Meshali MM. Novel Clove essential oil nanoemulgel tailored by Taguchi’s model and scaffold-based nanofibers: Phytopharmaceuticals with promising potential as cyclooxygenase-2 inhibitors in external inflammation. International Journal of Nanomedicine. 2020 Mar 30:2171-95.
  35. Farghaly Aly U, Abou-Taleb HA, Abdellatif AA, Sameh Tolba N. Formulation and evaluation of simvastatin polymeric nanoparticles loaded in hydrogel for optimum wound healing purpose. Drug design, development and therapy. 2019 May 10:1567-80.