title: Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin.
abstract: A brain drug delivery system for glioma chemotherapy based on transferrin-conjugated biodegradable polymersomes, Tf-PO-DOX, was made and evaluated with doxorubicin (DOX) as a model drug. Biodegradable polymersomes (PO) loaded with doxorubicin (DOX) were prepared by the nanoprecipitation method (PO-DOX) and then conjugated with transferrin (Tf) to yield Tf-PO-DOX with an average diameter of 107 nm and surface Tf molecule number per polymersome of approximately 35. Compared with PO-DOX and free DOX, Tf-PO-DOX demonstrated the strongest cytotoxicity against C6 glioma cells and the greatest intracellular delivery. It was shown in pharmacokinetic and brain distribution experiments that Tf-PO significantly enhanced brain delivery of DOX, especially the delivery of DOX into brain tumor cells. Pharmacodynamics results revealed a significant reduction of tumor volume and a significant increase of median survival time in the group of Tf-PO-DOX compared with those in saline control animals, animals treated with PO-DOX, and free DOX solution. By terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling, Tf-PO-DOX could extensively make tumor cell apoptosis. These results indicated that Tf-PO-DOX could significantly enhance the intracellular delivery of DOX in glioma and the chemotherapeutic effect of DOX for glioma rats.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China, 201203.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yu
authors.forename: Liangran
authors.initials: L
authors.lastname: Guo
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Shuaiqi
authors.initials: S
authors.lastname: Pan
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Ren
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Wen
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013997:Time Factors; D014018:Tissue Distribution; D014168:Transferrin / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D004337:Drug Carriers; D011108:Polymers; D014168:Transferrin; D004317:Doxorubicin