Anti-transferrin receptor-modified amphotericin B-loaded PLA-PEG nanoparticles cure Candidal meningitis and reduce drug toxicity

被引：40
作者：
Tang, Xiaolong [1 ,2 ,3 ]
Liang, Yong [4 ]
Zhu, Yongqiang [1 ,2 ,5 ]
Xie, Chunmei [6 ]
Yao, Aixia [1 ,2 ]
Chen, Li [1 ,2 ]
Jiang, Qinglin [1 ,2 ]
Liu, Tingting [1 ,2 ]
Wang, Xiaoyu [1 ,2 ]
Qian, Yunyun [1 ,2 ]
Wei, Jia [1 ,2 ]
Ni, Wenxuan [1 ,2 ]
Dai, Jingjing [1 ,2 ]
Jiang, Zhenyou [7 ,8 ]
Hou, Wei [3 ]
机构：
[1] Anhui Univ Sci & Technol, Huainan Peoples Hosp 1, Clin Lab, Huainan, Peoples R China
[2] Anhui Univ Sci & Technol, Coll Med, Affiliated Hosp 1, Huainan, Peoples R China
[3] Wuhan Univ, Sch Basic Med Sci, Inst Med Virol, State Key Lab Virol, Wuhan 430071, Peoples R China
[4] Xuzhou Med Coll, Huaian Hosp, Clin Lab, Huaian, Peoples R China
[5] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Med Genet, Wuhan 430074, Peoples R China
[6] Southern Med Univ, Sch Biotechnol, Guangzhou, Guangdong, Peoples R China
[7] Jinan Univ, Sch Med, Dept Microbiol & Immunol, Guangzhou 510632, Guangdong, Peoples R China
[8] Jinan Univ, Guangdong Key Lab Mol Immunol & Antibody Engn, Guangzhou 510632, Guangdong, Peoples R China
来源：
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2015年 / 10卷
关键词：
drug delivery; nanocarrier; amphotericin B; blood-brain barrier; transferrin receptor; IN-VITRO; FUNGAL-INFECTION; EFFICACY; MICELLES; SAFETY; MODEL;
D O I：
10.2147/IJN.S84656
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
Fatal fungal infections in central nervous system (CNS) can occur through hematogenous spread or direct extension. At present, hydrophobic amphotericin B (AMB) is the most effective antifungal drug in clinical trials. However, AMB is hydrophobic and therefore penetrates poorly into the CNS, and therapeutic levels of AMB are hard to achieve. The transferrin receptor (TfR/CD71) located at the blood-brain barrier mediates transferrin transcytosis. In order to enhance the receptor-mediated delivery of AMB into CNS with therapeutic level, an anti-TfR antibody (OX26)-modified AMB-loaded PLA (poly[lactic acid])-PEG (polyethylene glycol)-based micellar drug delivery system was constructed. The prepared OX26-modified AMB-loaded nanoparticles (OX26-AMB-NPs) showed significant reduction of CNS fungal burden and an increase of mouse survival time. In conclusion, OX26-AMB-NPs represent a promising novel drug delivery system for intracerebral fungal infection.
引用
收藏
页码：6227 / 6241
页数：15
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