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

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2024 Dec 10

PMID 39654804

Authors

Ting Shen

Mengxing Li

Baocheng Tian

Wei Liu

Lili Chu

Pengfei Yu

Huihui Zhou

Yanchun Han

Chen Ding

Sixiang Sai

Affiliations

Soon will be listed here.

Abstract

Introduction: 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 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.

References

Reese A, Yoneda A, Breger J, Beauvais A, Liu H, Griffith C . Loss of cell wall alpha(1-3) glucan affects Cryptococcus neoformans from ultrastructure to virulence. Mol Microbiol. 2007; 63(5):1385-98. PMC: 1864955. DOI: 10.1111/j.1365-2958.2006.05551.x. View

Dong Y, Feng S . In vitro and in vivo evaluation of methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles for small-molecule drug chemotherapy. Biomaterials. 2007; 28(28):4154-60. DOI: 10.1016/j.biomaterials.2007.05.026. View

Watkins R, Wu L, Zhang C, Davis R, Xu B . Natural product-based nanomedicine: recent advances and issues. Int J Nanomedicine. 2015; 10:6055-74. PMC: 4592057. DOI: 10.2147/IJN.S92162. View

Ruchel R, Margraf S . Rapid microscopical diagnosis of deep-seated mycoses following maceration of fresh specimens and staining with optical brighteners. Mycoses. 1993; 36(7-8):239-42. DOI: 10.1111/j.1439-0507.1993.tb00757.x. View

Wang X, Zhong X, Li J, Liu Z, Cheng L . Inorganic nanomaterials with rapid clearance for biomedical applications. Chem Soc Rev. 2021; 50(15):8669-8742. DOI: 10.1039/d0cs00461h. View

Gushiken A, Saharia K, Baddley J . Cryptococcosis. Infect Dis Clin North Am. 2021; 35(2):493-514. DOI: 10.1016/j.idc.2021.03.012. View

Allen T, Cullis P . Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2012; 65(1):36-48. DOI: 10.1016/j.addr.2012.09.037. View

Theuretzbacher U, Ihle F, Derendorf H . Pharmacokinetic/pharmacodynamic profile of voriconazole. Clin Pharmacokinet. 2006; 45(7):649-63. DOI: 10.2165/00003088-200645070-00002. View

de Sa F, Taveira S, Gelfuso G, Lima E, Gratieri T . Liposomal voriconazole (VOR) formulation for improved ocular delivery. Colloids Surf B Biointerfaces. 2015; 133:331-8. DOI: 10.1016/j.colsurfb.2015.06.036. View

10.

Stackova L, Stacko P, Klan P . Approach to a Substituted Heptamethine Cyanine Chain by the Ring Opening of Zincke Salts. J Am Chem Soc. 2019; 141(17):7155-7162. DOI: 10.1021/jacs.9b02537. View

11.

Gow N, Latge J, Munro C . The Fungal Cell Wall: Structure, Biosynthesis, and Function. Microbiol Spectr. 2017; 5(3). PMC: 11687499. DOI: 10.1128/microbiolspec.FUNK-0035-2016. View

12.

Yu C, He B, Xiong M, Zhang H, Yuan L, Ma L . The effect of hydrophilic and hydrophobic structure of amphiphilic polymeric micelles on their transport in epithelial MDCK cells. Biomaterials. 2013; 34(26):6284-98. DOI: 10.1016/j.biomaterials.2013.05.006. View

13.

Talapko J, Juzbasic M, Matijevic T, Pustijanac E, Bekic S, Kotris I . The Virulence Factors and Clinical Manifestations of Infection. J Fungi (Basel). 2021; 7(2). PMC: 7912069. DOI: 10.3390/jof7020079. View

14.

Iorio E, Torosantucci A, Bromuro C, Chiani P, Ferretti A, Giannini M . Candida albicans cell wall comprises a branched beta-D-(1-->6)-glucan with beta-D-(1-->3)-side chains. Carbohydr Res. 2008; 343(6):1050-61. DOI: 10.1016/j.carres.2008.02.020. View

15.

Patra J, Das G, Fraceto L, Campos E, Del Pilar Rodriguez-Torres M, Acosta-Torres L . Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018; 16(1):71. PMC: 6145203. DOI: 10.1186/s12951-018-0392-8. View

16.

Tran N, Ha D, Pham L, Vo T, Nguyen N, Tran C . Ag/SiO nanoparticles stabilization with lignin derived from rice husk for antifungal and antibacterial activities. Int J Biol Macromol. 2023; 230:123124. DOI: 10.1016/j.ijbiomac.2022.123124. View

17.

Roncero C, Valdivieso M, RIBAS J, Duran A . Effect of calcofluor white on chitin synthases from Saccharomyces cerevisiae. J Bacteriol. 1988; 170(4):1945-9. PMC: 211055. DOI: 10.1128/jb.170.4.1945-1949.1988. View

18.

Moen M, Lyseng-Williamson K, Scott L . Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections. Drugs. 2009; 69(3):361-92. DOI: 10.2165/00003495-200969030-00010. View

19.

Levine M, Chandrasekar P . Adverse effects of voriconazole: Over a decade of use. Clin Transplant. 2016; 30(11):1377-1386. DOI: 10.1111/ctr.12834. View

20.

Renzi D, de Almeida Campos L, Miranda E, Mainardes R, Abraham W, Grigoletto D . Nanoparticles as a Tool for Broadening Antifungal Activities. Curr Med Chem. 2020; 28(9):1841-1873. DOI: 10.2174/0929867327666200330143338. View