Emerging Lipid based Systems for Antifungal Delivery: A comprehensive review

Authors

  • Pallavi Suyal
  • Disha Dutta
  • Ramsha Aslam
  • Manoj Bisht

DOI:

https://doi.org/10.63682/jns.v14i32S.7310

Keywords:

Antifungal agents, lipid-based nanocarriers, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, drug delivery, fungal infections

Abstract

Aim: The increasing prevalence of fungal infections and the rise of antifungal resistance necessitate innovative drug delivery strategies to enhance therapeutic efficacy and minimize toxicity. This review aims to provide a comprehensive overview of emerging lipid-based delivery systems—such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid-drug conjugates—developed for efficient antifungal drug delivery.

Methodology: A systematic literature search was conducted across databases including PubMed, Scopus, and ScienceDirect, focusing on studies published between 2005 and 2025. The selected articles were screened for relevance to lipid-based antifungal drug delivery, formulation strategies, physicochemical characteristics, in vitro/in vivo efficacy, and toxicity profiles. Comparative evaluation was performed to assess the advantages and limitations of each system.

Results: Lipid-based formulations demonstrated superior drug encapsulation, improved solubility of poorly water-soluble antifungal agents (e.g., itraconazole, amphotericin B), sustained release profiles, and enhanced skin/mucosal penetration. Among these, NLCs and liposomes showed significant promise in reducing systemic toxicity and improving site-specific delivery. Novel hybrid and surface-functionalized lipid systems further enhanced antifungal selectivity and bioavailability, especially in dermal and mucosal applications.

Conclusion: Emerging lipid-based delivery systems represent a transformative approach in antifungal therapy, overcoming the limitations of conventional formulations. Their ability to enhance pharmacokinetic profiles, target infected tissues, and reduce drug resistance makes them promising candidates for future clinical applications. However, further translational studies and regulatory validations are warranted to ensure large-scale applicability and patient safety.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Abdelwahab, S. I., Taha, N., Sheikh, N., How, N., El-Sunousi, N., Abdullah, N., Eid, N., & Yagoub, N. U. (2013). Thymoquinone-loaded nanostructured lipid carriers: preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration. International Journal of Nanomedicine, 2163. https://doi.org/10.2147/ijn.s44108.

Aljaeid, B. M., & Hosny, K. M. (2016). Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity. International Journal of Nanomedicine, 11, 441–447.

Andonova, V., & Peneva, P. (2018). Characterization Methods for Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC). Current Pharmaceutical Design, 23(43), 6630–6642. https://doi.org/10.2174/1381612823666171115105721.

Araújo, J., Gonzalez-Mira, E., Egea, M. A., Garcia, M. L., & Souto, E. B. (2010). Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications. International Journal of Pharmaceutics, 393(1–2), 168–176. https://doi.org/10.1016/j.ijpharm.2010.03.034.

Averina, E. S., Müller, R. H., Popov, D. V., & Radnaeva, L. D. (2011). Physical and chemical stability of nanostructured lipid drug carriers (NLC) based on natural lipids from Baikal region (Siberia, Russia). Pharmazie, 66(5), 348–356. https://doi.org/10.1691/ph.2011.0326

Beloqui, A., Solinís, M. Á., Rodríguez-Gascón, A., Almeida, A. J., & Préat, V. (2016). Nanostructured lipid carriers: Promising drug delivery systems for future clinics. Nanomedicine: Nanotechnology, Biology, and Medicine, 12(1), 143–161. https://doi.org/10.1016/j.nano.2015.09.004.

Bhalekar, M. R., Upadhaya, P. G., & Madgulkar, A. R. (2016). Formulation and evaluation of ketoconazole loaded nanostructured lipid carriers for topical delivery. Asian Journal of Pharmaceutical Sciences, 11(3), 385–392.

Cordeiro, C., de Oliveira, M. D. S., & Chaud, M. V. (2019). Amphotericin B-loaded nanostructured lipid carriers: an innovative approach for topical delivery against fungal infections. Colloids and Surfaces B: Biointerfaces, 178, 390–397.

Chen, Y., Pan, L., Jiang, M., Li, D., & Jin, L. (2015). Nanostructured lipid carriers enhance the bioavailability and brain cancer inhibitory efficacy of curcumin both in vitro and in vivo. Drug Delivery, 23(4), 1383–1392. https://doi.org/10.3109/10717544.2015.1049719.

De Barros, D. P. C., Santos, R., Reed, P., Fonseca, L. P., & Oliva, A. (2022). Design of Quercetin-Loaded Natural Oil-Based nanostructured lipid carriers for the treatment of bacterial skin infections. Molecules, 27(24), 8818. https://doi.org/10.3390/molecules27248818.

Das, S., Ghosh, S., De, A. K., & Bera, T. (2017). Oral delivery of ursolic acid-loaded nanostructured lipid carrier coated with chitosan oligosaccharides: Development, characterization, in vitro and in vivo assessment for the therapy of leishmaniasis. International Journal of Biological Macromolecules, 102, 996–1008. https://doi.org/10.1016/j.ijbiomac.2017.04.098

De Carvalho, F. C., Bruschi, M. L., Evangelista, R. C., & Gremião, M. P. D. (2018). Mucoadhesive drug delivery systems. Brazilian Journal of Pharmaceutical Sciences, 46(1), 1–17.

Doktorovova, S., Shegokar, R., Martins-Lopes, P., Lopes, C. M., Müller, R. H., & Souto, E. B. (2014). Modified Rose Bengal-loaded solid lipid nanoparticles for photodynamic therapy: Evaluation of phototoxicity, skin irritation, and in vivo biodistribution. International Journal of Pharmaceutics, 452(1–2), 300–312. https://doi.org/10.1016/j.ijpharm.2013.12.026.

Ghasemiyeh, P., & Mohammadi-Samani, S. (2018). Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: Applications, advantages and disadvantages. Research in Pharmaceutical Sciences, 13(4), 288–303. https://doi.org/10.4103/1735-5362.235156.

Gupta, P. K., Mishra, N., & Rawat, A. (2018). Development and characterization of griseofulvin loaded nanostructured lipid carriers. Asian Journal of Pharmaceutics, 12(1), S145–S151.

Jain, A., Thakur, K., Kush, P., & Jain, A. (2021). Development and optimization of voriconazole loaded nanostructured lipid carriers for ocular delivery. Pharmaceutical Development and Technology, 26(6), 652–661.

Kumar, R., Rajesh, Y., Kaur, K., & Jain, S. (2014). Development and characterization of itraconazole loaded nanostructured lipid carriers for oral delivery. Journal of Drug Delivery Science and Technology, 24(4), 354–359.

Kovacevic A, Savic S, Vuleta G, Müller RH, Keck CM. 2011. Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure. Int J Pharm. 406:163–172.

Kaur, I. P., & Saraf, S. (2011). In vitro/in vivo efficacy of miconazole loaded lipid nanocarriers for vaginal candidiasis. Pharmaceutical Development and Technology, 16(4), 375–382.

Lombardi Borgia S, Regehly M, Sivaramakrishnan R, Mehnert W, Korting HC, Danker K, et al. 2005.

Lipid nanoparticles for skin penetration enhancement—correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy. J Control Release. 110:151–163.

Loo, C. H., Basri, M., Ismail, R., Lau, H. L. N., Tejo, B. A., Kanthimathi, M. S., & Hassan, H. A. (2013). Effect of compositions in nanostructured lipid carriers ( NLC ) on skin hydration and occlusion Effect of compositions in nanostructured lipid carriers ( NLC ) on skin hydration and occlusion. 9114. https://doi.org/10.2147/IJN.S35648.

Mehnert, W., & Mäder, K. (2012). Solid lipid nanoparticles: Production, characterization and applications. Advanced Drug Delivery Reviews, 64, 83–101. https://doi.org/10.1016/j.addr.2012.09.021.

Mukherjee, S., Ray, S., & Thakur, R. S. (2009). Solid lipid nanoparticles: A modern formulation approach in drug delivery system. Indian Journal of Pharmaceutical Sciences, 71(4), 349–358. https://doi.org/10.4103/0250-474X.57282.

Madane, R. G., & Mahajan, H. S. (2016). Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study. Drug Delivery, 23(4), 1326–1334. https://doi.org/10.3109/10717544.2014.975382

Makoni, P. A., Kasongo, K. W., & Walker, R. B. (2019). Short term stability testing of efavirenz-loaded solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions. Pharmaceutics, 11(8). https://doi.org/10.3390/pharmaceutics11080397

Naseri, N., Valizadeh, H., & Zakeri-Milani, P. (2015). Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application. Advanced Pharmaceutical Bulletin, 5(3), 305–313. https://doi.org/10.15171/apb.2015.043

Obeidat, W. M., Schwabe, K., Müller, R. H., & Keck, C. M. (2010). Preservation of nanostructured lipid carriers (NLC). European Journal of Pharmaceutics and Biopharmaceutics, 76(1), 56–67. https://doi.org/10.1016/j.ejpb.2010.05.001.

Pardeike, J., Hommoss, A., & Müller, R. H. (2009). Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. International Journal of Pharmaceutics, 366(1-2), 170–184. https://doi.org/10.1016/j.ijpharm.2008.10.003.

Poonia, N., Narang, J. K., Lather, V., Beg, S., Sharma, T., Singh, B., & Pandita, D. (2019). Resveratrol loaded functionalized nanostructured lipid carriers for breast cancer targeting: Systematic development, characterization and pharmacokinetic evaluation. Colloids and Surfaces B Biointerfaces, 181, 756–766. https://doi.org/10.1016/j.colsurfb.2019.06.004

Patel, R., Barot, B. S., Parejiya, P. B., & Shelat, P. K. (2012). Nanostructured lipid carriers for topical delivery of terbinafine hydrochloride. Journal of Pharmacy & Pharmacognosy Research, 1(1), 1–9.

Raju, M., Kunde, S. S., Auti, S. T., Kulkarni, Y. A., & Wairkar, S. (2021). Berberine loaded nanostructured lipid carrier for Alzheimer’s disease: Design, statistical optimization and enhanced in vivo performance. Life Sciences, 285, 119990. https://doi.org/10.1016/j.lfs.2021.119990.

Shangguan, M., Lu, Y., Qi, J., Han, J., Tian, Z., Xie, Y., Hu, F., Yuan, H., & Wu, W. (2013). Binary lipids-based nanostructured lipid carriers for improved oral bioavailability of silymarin. Journal of Biomaterials Applications, 28(6), 887–896. https://doi.org/10.1177/0885328213485141.

Souza, J. G., et al. (2011). Nanostructured lipid carrier systems for topical delivery of clotrimazole. International Journal of Pharmaceutics, 408(1–2), 204–213.

Schäfer-Korting M, Mehnert W, Korting HC. 2007. Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Rev. 59:427–443.

Souto, E. B., & Müller, R. H. (2008). Cosmetic features and applications of lipid nanoparticles (SLN®, NLC®). International Journal of Cosmetic Science, 30(3), 157–165. https://doi.org/10.1111/j.1468-2494.2008.00433.x

Souto, E. B., Baldim, I., Oliveira, W. P., Rao, R., Yadav, N., Gama, F. M., & Mahant, S. (2020). SLN and NLC for topical, dermal, and transdermal drug delivery. Expert Opinion on Drug Delivery, 17(3), 357–377. https://doi.org/10.1080/17425247.2020.1727883.

Souto, E. B., Wissing, S. A., Barbosa, C. M., & Müller, R. H. (2004). Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations. European Journal of Pharmaceutics and Biopharmaceutics, 58(1), 83–90. https://doi.org/10.1016/j.ejpb.2004.02.015

Taghipour, S., Kiasat, N., Shafiei, S., Halvaeezadeh, M., Rezaei-Matehkolaei, A., & Zarei Mahmoudabadi, A. (2018). Luliconazole, a new antifungal against Candida species isolated from different sources. Journal de Mycologie Medicale, 28(2), 374–378. https://doi.org/10.1016/j.mycmed.2017.11.004

Taghipour, S., Kiasat, N., Shafiei, S., Halvaeezadeh, M., Rezaei-Matehkolaei, A., & Zarei Mahmoudabadi, A. (2018). Luliconazole, a new antifungal against Candida species isolated from different sources. Journal de Mycologie Medicale, 28(2), 374–378. https://doi.org/10.1016/j.mycmed.2017.11.004.

Tan, S. W., Billa, N., Roberts, C. R., & Burley, J. C. (2010). Surfactant effects on the physical characteristics of Amphotericin B-containing nanostructured lipid carriers. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 372(1–3), 73–79. https://doi.org/10.1016/j.colsurfa.2010.09.030

Teeranachaideekul, V., Souto, E. B., Junyaprasert, V. B., & Müller, R. H. (2007). Cetyl palmitate-based NLC for topical delivery of Coenzyme Q10 - Development, physicochemical characterization and in vitro release studies. European Journal of Pharmaceutics and Biopharmaceutics, 67(1), 141–148. https://doi.org/10.1016/j.ejpb.2007.01.015

Thatipamula, R. P., Palem, C. R., Gannu, R., Mudragada, S., & Yamsani, M. R. (2011). Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers. DARU, Journal of Pharmaceutical Sciences, 19(1), 23–32.

Uner, M., Wissing, S. A., Yener, G., & Müller, R. H. (2005). Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for application of ascorbyl palmitate. Pharmazie, 60(8), 577–582.

Viegas, C., Patrício, A. B., Prata, J. M., Nadhman, A., Chintamaneni, P. K., & Fonte, P. (2023). Solid Lipid Nanoparticles vs. Nanostructured Lipid Carriers: A Comparative Review. Pharmaceutics, 15(6). https://doi.org/10.3390/pharmaceutics15061593.

Wissing, S. A., Kayser, O., & Müller, R. H. (2004). Solid lipid nanoparticles for parenteral drug delivery. Advanced Drug Delivery Reviews, 56(9), 1257–1272. https://doi.org/10.1016/j.addr.2003.12.002.

Wu, K. W., Sweeney, C., Dudhipala, N., Lakhani, P., Chaurasiya, N. D., Tekwani, B. L., & Majumdar, S. (2022). Correction to: Primaquine Loaded Solid Lipid Nanoparticles (SLN), Nanostructured Lipid Carriers (NLC), and Nanoemulsion (NE): Effect of Lipid Matrix and Surfactant on Drug Entrapment, in vitro Release, and ex vivo Hemolysis (AAPS PharmSciTech, (2021), 22,. AAPS PharmSciTech, 23(1), 1–23. https://doi.org/10.1208/s12249-021-02171-y

Zheng, M., Falkeborg, M., Zheng, Y., Yang, T., & Xu, X. (2013). Formulation and characterization of nanostructured lipid carriers containing a mixed lipids core. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 430, 76–84. https://doi.org/10.1016/j.colsurfa.2013.03.070.

Downloads

Published

2025-06-12

How to Cite

1.
Suyal P, Dutta D, Aslam R, Bisht M. Emerging Lipid based Systems for Antifungal Delivery: A comprehensive review. J Neonatal Surg [Internet]. 2025Jun.12 [cited 2025Jul.19];14(32S):77-89. Available from: https://jneonatalsurg.com/index.php/jns/article/view/7310