title: Enhanced Antifungal Activity by Ab-Modified Amphotericin B-Loaded Nanoparticles Using a pH-Responsive Block Copolymer.
abstract: Fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Amphotericin B (AMB), with broad-spectrum antifungal activity, has long been recognized as a powerful fungicidal drug, but its clinical toxicities mainly nephrotoxicity and poor solubility limit its wide application in clinical practice. The fungal metabolism along with the host immune response usually generates acidity at sites of infection, resulting in loss of AMB activity in a pH-dependent manner. Herein, we developed pH-responsive AMB-loaded and surface charge-switching poly(D,L-lactic-co-glycolic acid)-b-poly(L-histidine)-b-poly(ethylene glycol) (PLGA-PLH-PEG) nanoparticles for resolving the localized acidity problem and enhance the antifungal efficacy of AMB. Moreover, we modified AMB-encapsulated PLGA-PLH-PEG nanoparticles with anti-Candida albicans antibody (CDA) (CDA-AMB-NPs) to increase the targetability. Then, CDA-AMB-NPs were characterized in terms of physical characteristics, in vitro drug release, stability, drug encapsulation efficiency, and toxicity. Finally, the targetability and antifungal activity of CDA-AMB-NPs were investigated in vitro/in vivo. The result demonstrated that CDA-AMB-NPs significantly improve the targetability and bioavailability of AMB and thus improve its antifungal activity and reduce its toxicity. These NPs may become a good drug carrier for antifungal treatment.
authors.affiliation: Stem Cell Engineering Research Center, Anhui University of Science and Technology, Huainan, 232001, China, txljd2006@126.com.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Tang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Dai
authors.forename: Jun
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authors.lastname: Xie
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Ming
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authors.lastname: Zhu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Chunmei
authors.initials: C
authors.lastname: Xie
authors.forename: Aixia
authors.initials: A
authors.lastname: Yao
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Shulei
authors.initials: S
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.forename: Congjing
authors.initials: C
authors.lastname: Xu