Calcofluor White-Phosphatidylethanolamine Conjugate-Enhanced Ethosomal Delivery of Voriconazole for Targeting Candida albicans

Abstract

Ting Shen,1,* Mengxing Li,1,* Baocheng Tian,1,* Wei Liu,2 Lili Chu,3 Pengfei Yu,1 Huihui Zhou,4 Yanchun Han,1 Chen Ding,2 Sixiang Sai1 1School of Pharmacy, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 2College of Life and Health Science, Northeastern University, Shenyang, 110015, People’s Republic of China; 3Department of Pathology, Yantai Fushan District People’s Hospital, Yantai, Shandong, 265500, People’s Republic of China; 4Department of Pathology, Affiliated Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 266071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen Ding, College of Life and Health Sciences, Northeastern University, Shenyang, 110015, People’s Republic of China, Email [email protected] Sixiang Sai, School of Pharmacy, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China, Email [email protected]: The increasing prevalence of systemic fungal infections, especially among immunocompromised individuals, highlights the need for advancements in targeted and effective antifungal treatments. This study presents a novel nanomaterial, CFW-phosphatidylethanolamine conjugate (CFW-PEc), designed to enhance the delivery and efficacy of antifungal agents by targeting fungal cell walls through specific chitin binding. Ethosomes, lipid-based nanocarriers known for their ability to improve drug delivery across skin and cell membranes, were utilized in this study.Methods: The physicochemical characteristics of voriconazole-loaded CFW-PEc ethosomes (CFW-PEc-VRC-ethosomes) were examined, including particle size, zeta potential, and entrapment efficiency. Antifungal efficacy of CFW-PEc-VRC-ethosomes was evaluated, including antifungal activity in vitro, CFW-PEc-ethosomes cellular uptake, and models of animal infection and imaging analyses.Results: In vitro experiments demonstrated a concentration-dependent inhibition of C. albicans growth by CFW-PEc, with cell inhibition rates reaching nearly 100% at 256 μM. In vivo investigations confirmed a 5-fold reduction in fungal burden in the liver and a 7.8-fold reduction in the kidney compared to the control group following treatment with CFW-PEc (0.1 μM)-VRC-ethosomes. Imaging analyses also confirmed the extended tissue retention of fluorescent dye-loaded CFW-PEc-ethosomes in mice, further underscoring their potential for clinical use.Discussion: The targeted delivery of antifungal medications via ethosomes coated with CFW-PEc presents a promising strategy to improve antifungal effectiveness while reducing adverse effects, marking a significant advancement in fungal infection therapy.Keywords: CFW-phosphatidylethanolamine conjugate, antifungal agents, fungal cell walls, chitin binding, ethosomes

Keywords

• cfw-phosphatidylethanolamine conjugate
• antifungal agents
• fungal cell walls
• chitin binding
• ethosomes.