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Effect of intratumoral injection on the biodistribution and therapeutic potential of novel chemophor EL-modified single-walled nanotube loading doxorubicin.

Abstract
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.
AuthorsHongzhuo Liu, Hui Xu, Yan Wang, Zhonggui He, Sanming Li
JournalDrug development and industrial pharmacy (Drug Dev Ind Pharm) Vol. 38 Issue 9 Pg. 1031-8 (Sep 2012) ISSN: 1520-5762 [Electronic] England
PMID22794192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibiotics, Antineoplastic
  • Nanotubes, Carbon
  • Pharmaceutical Vehicles
  • cremophor EL
  • Doxorubicin
  • Glycerol
Topics
  • Absorption
  • Animals
  • Antibiotics, Antineoplastic (administration & dosage, metabolism, pharmacokinetics, therapeutic use)
  • Cell Line, Tumor
  • Doxorubicin (administration & dosage, metabolism, pharmacokinetics, therapeutic use)
  • Drug Compounding
  • Drug Delivery Systems
  • Female
  • Glycerol (adverse effects, analogs & derivatives, chemistry)
  • Hydrophobic and Hydrophilic Interactions
  • Injections, Intralesional
  • Mice
  • Mice, Inbred ICR
  • Nanotubes, Carbon (adverse effects, chemistry)
  • Neoplasm Transplantation
  • Pharmaceutical Vehicles (adverse effects, chemistry)
  • Sarcoma 180 (drug therapy, metabolism, pathology)
  • Solubility
  • Tissue Distribution
  • Tumor Burden (drug effects)

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