Response Surface Methodology-Guided Optimization of Flucytosine Nanoemulsion for Enhanced Antifungal Performance
By: Priya Tiwari, Shipra Verma and Gajendra Saini
References
- Ali, A., Chiang, Y. W., & Santos, R. M. (2022). X-ray diffraction techniques for mineral characterization: A review for engineers of the fundamentals, applications, and research directions. Minerals, 12(2), 205.
https://doi.org/https://doi.org/10.3390/min12020205 - Anwer, M. K., Aldawsari, M. F., Iqbal, M., Almutairy, B. K., Soliman, G. A., & Aboudzadeh, M. A. (2023). Diosmin-loaded nanoemulsion-based gel formulation: Development, optimization, wound healing and anti-inflammatory studies. Gels, 9(2), 95.
https://doi.org/10.3390/gels9020095 - Beg, S., Swain, S., Singh, H. P., Patra, C. N., & Rao, M. E. B. (2012). Development, optimization, and characterization of solid self-nanoemulsifying drug delivery systems of valsartan using porous carriers. Aaps Pharmscitech, 13, 1416–1427.
- Clapham, D., Belissa, E., Inghelbrecht, S., Pensé-Lhéritier, A.-M., Ruiz, F., Sheehan, L., Shine, M., Vallet, T., Walsh, J., & Tuleu, C. (2023). A guide to best practice in sensory analysis of pharmaceutical formulations. Pharmaceutics, 15(9), 2319.
https://doi.org/10.3390/pharmaceutics15092319 - Cong, Y., Du, C., Wang, M., Jiang, Z., & Wang, M. (2021). Solubility of 5-fluorocytosine in different pure and binary mixed solvents: measurement, model correlation, solvent effect, and preferential solvation. Journal of Chemical & Engineering Data, 66(8), 3090–3100.
https://doi.org/https://doi.org/10.1021/acs.jced.1c00206 - Delma, F. Z., Al-Hatmi, A. M. S., Brüggemann, R. J. M., Melchers, W. J. G., de Hoog, S., Verweij, P. E., & Buil, J. B. (2021). Molecular mechanisms of 5-fluorocytosine resistance in yeasts and filamentous fungi. Journal of Fungi, 7(11), 909.
https://doi.org/10.3390/jof7110909 - Denning, D. W. (2024). Global incidence and mortality of severe fungal disease. The Lancet Infectious Diseases, 24(7), e428–e438.
https://doi.org/10.1016/S1473-3099(23)00692-8 - Goyal, G., Garg, T., Malik, B., Chauhan, G., Rath, G., & Goyal, A. K. (2015). Development and characterization of niosomal gel for topical delivery of benzoyl peroxide. Drug Delivery, 22(8), 1027–1042.
https://doi.org/10.3109/10717544.2013.855277 - Hurt, W. J., Harrison, T. S., Molloy, S. F., & Bicanic, T. A. (2021). Combination therapy for HIV-associated cryptococcal meningitis—a success story. Journal of Fungi, 7(12), 1098.
https://doi.org/10.3390/jof7121098 - Jacob, S., Kather, F. S., Boddu, S. H. S., Shah, J., & Nair, A. B. (2024). Innovations in nanoemulsion technology: enhancing drug delivery for oral, parenteral, and ophthalmic applications. Pharmaceutics, 16(10), 1333.
https://doi.org/10.3390/pharmaceutics16101333 - Jarvis, J. N., Lawrence, D. S., Meya, D. B., Kagimu, E., Kasibante, J., Mpoza, E., Rutakingirwa, M. K., Ssebambulidde, K., Tugume, L., & Rhein, J. (2022). Single-dose liposomal amphotericin B treatment for cryptococcal meningitis. New England Journal of Medicine, 386(12), 1109–1120.
https://doi.org/10.1056/NEJMc2206274 - Kamdi, D. B., Yerne, H. M., & Patil, S. R. (2020). Development and Validation of UV Spectroscopic Method for Estimation of Fluconazole in Tablet Dosage Form. Am. J. PharmTech Res., 10(01), 83–92.
https://doi.org/10.46624/ajptr.2020.v10.i1.008 - Khani, S., Keyhanfar, F., & Amani, A. (2016). Design and evaluation of oral nanoemulsion drug delivery system of mebudipine. Drug Delivery, 23(6), 2035–2043.
https://doi.org/10.3109/10717544.2015.1088597 - Kumar, S., Ali, J., & Baboota, S. (2016). Design Expert® supported optimization and predictive analysis of selegiline nanoemulsion via the olfactory region with enhanced behavioural performance in Parkinson's disease. Nanotechnology, 27(43), 435101.
https://doi.org/10.1088/0957-4484/27/43/435101 - Linder, K. A., Kauffman, C. A., & Miceli, M. H. (2023). Blastomycosis: a review of mycological and clinical aspects. Journal of Fungi, 9(1), 117.
https://doi.org/10.3390/jof9010117 - Liu, D., Zhou, R., & Gao, X. (2025). Recent innovations and challenges in the treatment of fungal infections. Frontiers in Cellular and Infection Microbiology, 15, 1676009.
https://doi.org/10.3389/fcimb.2025.1676009 - McHale, T. C., Boulware, D. R., Kasibante, J., Ssebambulidde, K., Skipper, C. P., & Abassi, M. (2023). Diagnosis and management of cryptococcal meningitis in HIV-infected adults. Clinical Microbiology Reviews, 36(4), e00156–22.
https://doi.org/10.1128/cmr.00156-22 - Miot, J., Leong, T., Takuva, S., Parrish, A., & Dawood, H. (2021). Cost-effectiveness analysis of flucytosine as induction therapy in the treatment of cryptococcal meningitis in HIV-infected adults in South Africa. BMC Health Services Research, 21, 1–11.
https://doi.org/10.1186/s12913-021-06268-9 - Monograph, U. O. (2014). United States Pharmacopeial Convention. Rockville, MD, 3224.
- Nikolaev, B., Yakovleva, L., Fedorov, V., Li, H., Gao, H., & Shevtsov, M. (2023). Nano-and microemulsions in biomedicine: From theory to practice. Pharmaceutics, 15(7), 1989.
https://doi.org/10.3390/pharmaceutics15071989 Abstract - Pangeni, R., Sharma, S., Mustafa, G., Ali, J., & Baboota, S. (2014). Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson's disease by reducing oxidative stress. Nanotechnology, 25(48), 485102.
https://doi.org/10.1088/0957-4484/25/48/485102 - Patel, P., Ahir, K., Patel, V., Manani, L., & Patel, C. (2015). Drug-Excipient compatibility studies: First step for dosage form development. The Pharma Innovation, 4(5, Part A), 14.
- Rai, M., Ingle, A. P., & Pandit, R. (2021). Nanoemulsions as antifungal agents: Mechanisms, efficacy, and future perspectives. Journal of Applied Microbiology, 131(1), 3–18.
https://doi.org/https://doi.org/10.1111/jam.14989 - Rampado, R., & Peer, D. (2023). Design of experiments in the optimization of nanoparticle-based drug delivery systems. Journal of Controlled Release, 358, 398–419.
- Rasmussen, M. K., Pedersen, J. N., & Marie, R. (2020). Size and surface charge characterization of nanoparticles with a salt gradient. Nature Communications, 11(1), 2337.
https://doi.org/10.1038/s41467-020-15889-3 - Safhi, A. Y., Naveen, N. R., Rolla, K. J., Bhavani, P. D., Kurakula, M., Hosny, K. M., Abualsunun, W. A., Alissa, M., Alsalhi, A., & Alahmadi, A. A. (2023). Enhancement of antifungal activity and transdermal delivery of 5-flucytosine via tailored spanlastic nanovesicles: statistical optimization, in-vitro characterization, and in-vivo biodistribution study. Frontiers in Pharmacology, 14, 1321517.
https://doi.org/https://doi.org/10.3389/fphar.2023.1321517 - Sastré-Velásquez, L. E., Dallemulle, A., Kühbacher, A., Baldin, C., Alcazar-Fuoli, L., Niedrig, A., Müller, C., & Gsaller, F. (2022). The fungal expel of 5-fluorocytosine derived fluoropyrimidines mitigates its antifungal activity and generates a cytotoxic environment. PLoS Pathogens, 18(12), e1011066.
- Shaker, D. S., Ishak, R. A. H., Ghoneim, A., & Elhuoni, M. A. (2019). Nanoemulsion: A review on mechanisms for the transdermal delivery of hydrophobic and hydrophilic drugs. Scientia Pharmaceutica, 87(3), 17.
https://doi.org/10.3390/scipharm87030017 - Shi, Y., Zhang, M., Chen, K., & Wang, M. (2022). Nanoemulsion prepared by high pressure homogenization method as a good carrier for Sichuan pepper essential oil: Preparation, stability, and bioactivity. Lwt, 154, 112779.
https://doi.org/10.1016/j.lwt.2021.112779 - Sigera, L. S. M., & Denning, D. W. (2023). Flucytosine and its clinical usage. Therapeutic Advances in Infectious Disease, 10, 20499361231161388.
https://doi.org/https://doi.org/10.1177/20499361231161 - Tayeb, H. H., Felimban, R., Almaghrabi, S., & Hasaballah, N. (2021). Nanoemulsions: Formulation, characterization, biological fate, and potential role against COVID-19 and other viral outbreaks. Colloid and Interface Science Communications, 45, 100533.
https://doi.org/10.1016/j.colcom.2021.100533 - Tkachenko, Y., & Niedzielski, P. (2022). FTIR as a method for qualitative assessment of solid samples in geochemical research: a review. Molecules, 27(24), 8846.
https://doi.org/https://doi.org/10.3390/molecules27248846 - Vishwas, S., Kumar, R., Awasthi, A., Corrie, L., Bashir, B., Khursheed, R., Ramanunny, A. K., Gulati, M., Singh, T. G., & Gupta, G. (2024). Formulation and optimization of fisetin nanoemulsion for the treatment of Alzheimer's disease in rats: Pharmacokinetic and pharmacodynamic assessment. Journal of Drug Delivery Science and Technology, 101, 106269.
https://doi.org/https://doi.org/10.1016/j.jddst.2024.106269 - Yalkowsky, S. H., & Alantary, D. (2018). Estimation of melting points of organics. Journal of Pharmaceutical Sciences, 107(5), 1211–1227.
https://doi.org/10.1016/j.xphs.2017.12.013
DOI: https://doi.org/10.2478/afpuc-2026-0002 | Journal eISSN: 2453-6725
Language: English
Submitted on: Aug 22, 2024
Accepted on: Oct 8, 2024
Published on: Jun 24, 2026
Published by: Comenius University in Bratislava, Faculty of Pharmacy
In partnership with: Paradigm Publishing Services
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© 2026 Priya Tiwari, Shipra Verma, Gajendra Saini, published by Comenius University in Bratislava, Faculty of Pharmacy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.