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

• Published in: International journal of nanomedicine 2015-01, Vol.10 (default), p.6227-6241
• Main Authors: Tang, Xiaolong, Liang, Yong, Zhu, Yongqiang, Xie, Chunmei, Yao, Aixia, Chen, Li, Jiang, Qinglin, Liu, Tingting, Wang, Xiaoyu, Qian, Yunyun, Wei, Jia, Ni, Wenxuan, Dai, Jingjing, Jiang, Zhenyou, Hou, Wei
• Format: Article
• Language: English
• Subjects: Amphotericin B; Amphotericin B - administration & dosage; Amphotericin B - chemistry; Analysis; Animals; Antibodies, Monoclonal - immunology; Antifungal Agents - administration & dosage; Antifungal Agents - chemistry; Candida glabrata - pathogenicity; Candidiasis - drug therapy; Candidiasis - microbiology; Drug Delivery Systems; Drug therapy; Drug-Related Side Effects and Adverse Reactions; Drugs; Erythrocytes - drug effects; Erythrocytes - microbiology; Health aspects; Meningitis; Meningitis - drug therapy; Meningitis - microbiology; Mice; Mice, Inbred BALB C; Micelles; Mycoses; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Original Research; Polyethylene glycol; Polyethylene Glycols - chemistry; Rabbits; Receptors, Transferrin - antagonists & inhibitors; Receptors, Transferrin - immunology; Transferrin - metabolism; Vehicles
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S84656

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.