Effect of intratumoral injection on the biodistribution and therapeutic potential of novel chemophor EL-modified single-walled nanotube loading doxorubicin.
The purpose of this study is to evaluate in vivo efficacy and loco-regional distribution of a doxorubicin (DOX)-loaded Polyoxyl 35 Castor Oil (Cremophor EL, CrEL) noncovalent modified single-walled carbon nanotubes (SWNTs) formulation in a sarcoma tumor model after intratumoral injection. The drug loaded SWNTs were successfully prepared via physical absorption, which was confirmed by UV-vis-NIR absorbance spectra and dynamic light scattering assay. Solid tumor models were obtained by injecting mouse sarcoma 180 cells into the thighs of ICR mice. CrEL-SWNTs-DOX, CrEL-SWNTs, free DOX and saline (control) were intratumorally injected after 5 days post transplantation. The biodistribution studies demonstrated that intratumoral delivery of CrEL-SWNTs-DOX resulted in longer drug retention time in tumor, higher tumor level (27.6-fold than that of free DOX), as well as less accumulation in other solid tissues, especially in heart. Furthermore, in vivo anti-tumor activity results showed that CrEL-SWNTs-DOX could effectively suppress the tumor growth than free DOX and the control, attributing to its enhanced intratumoral DOX level. The histopathological findings revealed that the new carbon nanomaterials were a safe vehicle for topical drug delivery systems. It is concluded that this noncovalent modification of carbon nanotubes by CrEL for anticancer agents might be a promising alternative for cancer treatment.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Hongzhuo
H
Liu
Hui
H
Xu
Yan
Y
Wang
Zhonggui
Z
He
Sanming
S
Li
D000042:Absorption; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005260:Female; D005990:Glycerol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D015552:Injections, Intralesional; D051379:Mice; D008813:Mice, Inbred ICR; D037742:Nanotubes, Carbon / Q000009:adverse effects / Q000737:chemistry*; D009368:Neoplasm Transplantation; D014677:Pharmaceutical Vehicles / Q000009:adverse effects / Q000737:chemistry*; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D037742:Nanotubes, Carbon; D014677:Pharmaceutical Vehicles; C000515:cremophor EL; D004317:Doxorubicin; D005990:Glycerol