Growth inhibition against intracranial C6 glioma cells by stereotactic delivery of BCNU by controlled release from poly(D,L-lactic acid) nanoparticles.
Transferrin (Tf), an iron-transporting serum glycoprotein, which binds to receptors expressed at the surface of most proliferating cells with particularly high expression on erythroblasts and cancer cells, was chosen as the ligand to develop BCNU-loaded biodegradable poly(D,L-lactic acid) nanoparticles (NPs) containing a ligand, which specifically binds to glioma cells, and their anti-tumor ability was evaluated using a C6 glioma model. In vitro drug release behavior demonstrated that BCNU-loaded PLA NPs show certain sustained release characteristics. NPs with low molecular weight PLA showed a higher burst effect and a significantly faster drug release from PLA samples. The biodistribution of Tf-coated nanoparticles investigated by 99Tc-labeled SPECT showed that the surface-containing transferrin PLA nanoparticles were concentrated in the brain and no radioactive foci could be found outside the brain. Inhibition of tumor growth in the C6 tumor-bearing animal model showed that BCNU-loaded PLA NPs had stronger cytotoxicity and prolonged the average survival time of rats. Especially when treated at an early stage with a higher dosage of NPs, the average survival time of rats was prolonged 88.37%. Furthermore, one rat maintained normal behavior continuously for an observation period of up to 60 days.
Kang
ChunSheng
C
School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China PR.
Yuan
XuBo
X
Zhong
Yue
Y
Pu
PeiYu
P
Guo
YanShuang
Y
Albadany
Ammar
A
Yu
ShiZhu
S
Zhang
ZhiYong
Z
Li
YanHe
Y
Chang
Jin
J
Sheng
Jing
J
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002330:Carmustine / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques
D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D002330:Carmustine