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


CONCLUSIONS
Chitosan/GMO nanostructures containing PTX are safe and effective administered locally or intravenously. Partially supported by DOD Award BC045664.
Trickler
W J
WJ
Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, 2500 California Plaza, Omaha, Nebraska 68178, USA.
Nagvekar
A A
AA
Dash
A K
AK
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D049329:Nanostructures; D017239:Paclitaxel / Q000493:pharmacokinetics*; D013347:Subcellular Fractions / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D048271:Chitosan; D017239:Paclitaxel