Antifungal efficacy of itraconazole-loaded TPGS-b-(PCL-ran-PGA) nanoparticles.
This research was conducted to formulate biodegradable itraconazole (ITZ)-loaded d-a-tocopheryl polyethylene glycol 1000 succinate-b-poly(e-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA); TPP) nanoparticles (NPs) (designed as ITZ-loaded TPP NPs) to improve antifungal efficacy. ITZ-loaded TPP NPs were prepared by a modified double-emulsion method, and their size distribution, morphology, zeta potential, drug encapsulation efficiency, drug-release profile, and antifungal effects were characterized. The cytotoxicity of ITZ-loaded-TPP NPs on HeLa cells and fibroblasts was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The in vivo antifungal activity of ITZ-loaded-TPP NPs was examined in mice by administrating 5×10(5) colony forming units of Candida albicans through the tail vein. The survival rate and survival time of the mice was observed. The fungal count and pathology of lung tissue was analyzed. The data showed that ITZ-loaded-TPP NPs have size of 265±5.8 nm, zeta potential of -31±0.5 mV, high encapsulation efficiency (95%), and extended drug-release profile. ITZ-loaded-TPP NPs at a high concentration of 25 mg/mL had no cytotoxicity on HeLa cells and fibroblasts. Furthermore, ITZ-loaded-TPP NPs achieved a higher level of antifungal activity both in vitro and in vivo. The survival rate and duration was higher in mice treated by ITZ-loaded-TPP NPs than in the other groups (P<0.05). In conclusion, ITZ-loaded-TPP NPs significantly improved ITZ bioavailability by increasing its aqueous dispersibility and extending the duration of drug release, thereby improving the antifungal efficacy of the ITZ agent.
Institute of Virology, School of Medicine, State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei, People's Republic of China ; The Shenzhen Key Lab of Gene and Antibody Therapy, Center for Biotech and Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, People's Republic of China.
Lixin
L
Qiu
Institute of Virology, School of Medicine, State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei, People's Republic of China ; The Clinical Laboratory, Wuhan No 1 Hospital, Wuhan, Hubei, People's Republic of China.
Bicheng
B
Hu
The Shenzhen Key Lab of Gene and Antibody Therapy, Center for Biotech and Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, People's Republic of China ; School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.
Hongbo
H
Chen
Department of Plant Pathology and Microbiology, Iowa State University, Ames, IA, USA.
Shanshan
S
Li
The Shenzhen Key Lab of Gene and Antibody Therapy, Center for Biotech and Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, People's Republic of China ; School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.
Yuqian
Y
Hu
The Shenzhen Key Lab of Gene and Antibody Therapy, Center for Biotech and Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, People's Republic of China ; School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.
Yi
Y
Zheng
Institute of Virology, School of Medicine, State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei, People's Republic of China.
Xinxing
X
Wu
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D017964:Itraconazole / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity
D000935:Antifungal Agents; D014810:Vitamin E; D017964:Itraconazole; D011092:Polyethylene Glycols; C014225:tocophersolan
Candida albicans; TPGS-b-(PCL-ran-PGA) (TPP); antifungal; itraconazole (ITZ); nanoparticles (NPs)