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Enhanced antifungal effects of amphotericin B-TPGS-b-(PCL-ran-PGA) nanoparticles in vitro and in vivo

Authors Tang X, Zhu H, Sun L, Hou W, Cai S, Zhang R, Liu F

Received 23 July 2014

Accepted for publication 14 September 2014

Published 24 November 2014 Volume 2014:9(1) Pages 5403—5413


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Carlos Rinaldi

Xiaolong Tang,1,2,* He Zhu,3,* Ledong Sun,4,* Wei Hou,2 Shuyu Cai,1 Rongbo Zhang,1 Feng Liu5

1Stem Cell Engineering Research Center, School of Medicine, Anhui University of Science and Technology, Huainan, People’s Republic of China; 2State Key Laboratory of Virology, Life Sciences College, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Institute of Skin Damage and Repair, General Hospital of Beijing Military Command, Beijing, People’s Republic of China; 4Department of Dermatology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 5Department of Anesthesiology, Children’s Hospital, Chongqing Medical University; Key Laboratory of Child Development and Disorders of the Ministry of Education, Chongqing, People’s Republic of China

*These authors contributed equally to this work

Background: Amphotericin B (AMB) is a polyene antibiotic with broad spectrum antifungal activity, but its clinical toxicities and poor solubility limit the wide application of AMB in clinical practice. Recently, new drug-loaded nanoparticles (NPs) – diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (PLGA-TPGS) – have received special attention for their reduced toxicity, and increased effectiveness of drug has also been reported. This study aimed to develop AMB-loaded PLGA-TPGS nanoparticles (AMB-NPs) and evaluate their antifungal effects in vitro and in vivo.
Methods: AMB-NPs were prepared with a modified nanoprecipitation method and then characterized in terms of physical characteristics, in vitro drug release, stability, drug-encapsulation efficiency, and toxicity. Finally, the antifungal activity of AMB-NPs was investigated in vitro and in vivo.
Results: AMB-NPs were stable and spherical, with an average size of around 110 nm; the entrapment efficacy was closed to 85%, and their release exhibited a typically biphasic pattern. The actual minimum inhibitory concentration of AMB-NPs against Candida albicans was significantly lower than that of free AMB, and AMB-NPs were less toxic on blood cells. In vivo experiments indicated that AMB-NPs achieved significantly better and prolonged antifungal effects when compared with free AMB.
Conclusion: The AMB-PLGA-TPGS NP system significantly improves the AMB bioavailability by improving its antifungal activities and reducing its toxicity, and thus, these NPs may become a good drug carrier for antifungal treatment.

Keywords: drug delivery, anti-infection, nanocarrier, C. albicans, amphotericin B

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