The in vitro sub-cellular localization and in vivo efficacy of novel chitosan/GMO nanostructures containing paclitaxel.

Abstract

PURPOSE:

To determine the in vitro sub-cellular localization and in vivo efficacy of chitosan/GMO nanostructures containing paclitaxel (PTX) compared to a conventional PTX treatment (Taxol).

METHODS:

The sub-cellular localization of coumarin-6 labeled chitosan/GMO nanostructures was determined by confocal microscopy in MDA-MB-231 cells. The antitumor efficacy was evaluated in two separate studies using FOX-Chase (CB17) SCID Female-Mice MDA-MB-231 xenograph model. Treatments consisted of intravenous Taxol or chitosan/GMO nanostructures with or without PTX, local intra-tumor bolus of Taxol or chitosan/GMO nanostructures with or without PTX. The tumor diameter and animal weight was monitored at various intervals. Histopathological changes were evaluated in end-point tumors.

RESULTS:

The tumor diameter increased at a constant rate for all the groups between days 7-14. After a single intratumoral bolus dose of chitosan/GMO containing PTX showed significant reduction in tumor diameter on day 15 when compared to control, placebo and intravenous PTX administration. The tumor diameter reached a maximal decrease (4-fold) by day 18, and the difference was reduced to approximately 2-fold by day 21. Qualitatively similar results were observed in a separate study containing PTX when administered intravenously.

CONCLUSION:

Chitosan/GMO nanostructures containing PTX are safe and effective administered locally or intravenously. Partially supported by DOD Award BC045664.

• Authors: W J Trickler, A A Nagvekar, A K Dash
• Journal: Pharmaceutical research (Pharm Res) Vol. 26 Issue 8 Pg. 1963-73 (Aug 2009) ISSN: 1573-904X [Electronic] United States
• PMID: 19455409 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• Chitosan
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacokinetics)
• Cell Line, Tumor
• Chitosan (pharmacokinetics)
• Female
• Humans
• Mice
• Mice, SCID
• Microscopy, Confocal
• Nanostructures
• Paclitaxel (pharmacokinetics)
• Subcellular Fractions (metabolism)