Enhancing Antifungal Efficacy and Stability of Nystatin Liposomes Through Chitosan and Alginate Layer-by-Layer Coating: In vitro Studies Against Candida albicans

Evi Sulastri,1,2 Maya Nurul Rahma,1 Yedi Herdiana,1 Khaled M Elamin,3 Ahmed Fouad Abdelwahab Mohammed,4 Safwat A Mahmoud,5 Nasrul Wathoni1,6 1Department of Pharmaceutics and Pharmaceutical Technology, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 2Departement of Pharmacy, Faculty of Mathematics and Natural Sciences, Tadulako University, Palu, Central Sulawesi, 94118, Indonesia; 3Graduated School of Pharmaceutical Science, Kumamoto University, Kumamoto, 862-0973, Japan; 4Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt; 5Center for Scientific Research and Entrepreneurship, Northern Border University, Arar, 73213, Saudi Arabia; 6Functional Nano Powder University Centre of Excellence (Finder Ucoe), Universitas Padjadjaran, Sumedang, 45363, IndonesiaCorrespondence: Nasrul Wathoni, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, 45363, Indonesia, Tel +62-22-842-888-888, Email [email protected]: Candidiasis, predominantly caused by Candida albicans, poses a significant global health challenge, especially in tropical regions. Nystatin is a potent antifungal agent that is hindered by its low solubility and permeability, limiting its clinical efficacy.Methods: This study aimed to investigate the potential of a layer-by-layer (LBL) coating system, employing chitosan and alginate, to improve the stability, entrapment efficiency (%EE), and antifungal efficacy of nystatin-loaded liposomes against Candida albicans. Nystatin liposomes were synthesized via a thin-film hydration method and subsequently coated with varying ratios of chitosan and alginate using the LBL technique. The optimized formulations were characterized in terms of their particle size, zeta potential, %EE, and morphology. Furthermore, in vitro release dynamics, antifungal activity through Minimum Inhibitory Concentration (MIC) assays, and stability tests at 4°C were conducted.Results: The optimal formulation, designated as NA7-Ch3-Nys-Lip, exhibited a significant improvement in %EE (61.61 ± 1.60% to 83.77 ± 2.00%), enhanced antifungal activity (MIC value of 0.732 μg/mL), and superior stability compared to uncoated liposomes. The LBL system facilitated controlled drug release and maintained desirable particle characteristics under prolonged storage conditions.Conclusion: This study successfully demonstrated that LBL-coated nystatin liposomes significantly enhanced the antifungal activity, stability, and delivery efficiency of the drug. This novel formulation strategy offers a promising approach to overcome the limitations of conventional antifungal therapies, potentially improving the treatment of fungal infections.Keywords: Candida albicans, nystatin, layer by layer liposomes, antifungal