Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats.
The blood-brain barrier (BBB) and multidrug resistance (MDR) are the main causes for poor prognosis of glioma patients after chemotherapy. To explore the way for settling this problem, in this study, a novel antitumor agent loaded drug delivery system, lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine (Lf-PO-Dox/Tet), integrating both BBB and glioma-targeting moiety and MDR inhibitor, was designed and its chemotherapy for glioma rats was evaluated. Biodegradable polymersome (PO) encapsulating both doxorubicin (Dox) and tetrandrine (Tet) was prepared by the thin-film hydration method (PO-Dox/Tet) and then conjugated with lactoferrin (Lf) to yield Lf-PO-Dox/Tet with an average diameter around 220 nm and surface Lf molecule number per polymersome around 40. Compared with PO-DOX, PO-Dox/Tet, and Lf-PO-Dox, Lf-PO-Dox/Tet demonstrated the strongest cytotoxicity against C6 glioma cells and the greatest uptake index by C6 cells. In vivo imaging analysis indicated that Lf-PO labeled with a near-infrared dye could enter the brain and accumulate at the tumor site. Pharmacokinetics and tissue distribution results also showed that Lf-PO-Dox/Tet accumulated more in the right hemisphere than other groups of polymersomes. Pharmacodynamics results revealed that tumor volume of the Lf-PO-Dox/Tet group was significantly smaller than that of other therapeutic groups, and the median survival time of Lf-PO-Dox/Tet group was longer than that of Lf-PO-Dox group and significantly longer than those of the other three therapeutic groups. These results suggested that Lf-PO-Dox/Tet could have therapeutic potential for gliomas.
School of Pharmacy, Fudan University, Shanghai, PR China.
Zhiqing
Z
Pang
Liang
L
Feng
Rongrong
R
Hua
Jun
J
Chen
Huile
H
Gao
Shuaiqi
S
Pan
Xinguo
X
Jiang
Peng
P
Zhang
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D044182:Benzylisoquinolines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D007781:Lactoferrin / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D044182:Benzylisoquinolines; D011108:Polymers; C009438:tetrandrine; D004317:Doxorubicin; D007781:Lactoferrin