Anti-transferrin receptor-modified amphotericin B-loaded PLA-PEG nanoparticles cure Candidal meningitis and reduce drug toxicity.
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.
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China ; State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, People's Republic of China.
Xiaolong
X
Tang
Clinical Laboratory, Huai'an Hospital Affiliated of Xuzhou Medical College, Huaian, People's Republic of China.
Yong
Y
Liang
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China ; Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Yongqiang
Y
Zhu
School of Biotechnology, Southern Medical University, Guangzhou, People's Republic of China.
Chunmei
C
Xie
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China.
Aixia
A
Yao
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China.
Li
L
Chen
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China.
Qinglin
Q
Jiang
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China.
Tingting
T
Liu
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China.
Xiaoyu
X
Wang
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China.
Yunyun
Y
Qian
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China.
Jia
J
Wei
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China.
Wenxuan
W
Ni
Clinical Laboratory, Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, People's Republic of China.
Jingjing
J
Dai
Department of Microbiology and Immunology, School of Medicine, Jinan University, Guangzhou, People's Republic of China ; Guangdong Key Laboratory of Molecular Immunology and Antibody Engineering, Jinan University, Guangzhou, People's Republic of China.
Zhenyou
Z
Jiang
State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, People's Republic of China.
Wei
W
Hou
D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry; D041221:Candida glabrata / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D016503:Drug Delivery Systems; D064420:Drug-Related Side Effects and Adverse Reactions; D004912:Erythrocytes / Q000187:drug effects / Q000382:microbiology; D008581:Meningitis / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors* / Q000276:immunology; D014168:Transferrin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000935:Antifungal Agents; D008823:Micelles; D011990:Receptors, Transferrin; D014168:Transferrin; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D000666:Amphotericin B
amphotericin B; blood–brain barrier; drug delivery; nanocarrier; transferrin receptor