Antitumor Efficacy, Tumor Distribution and Blood Pharmacokinetics of Chitosan/Glyceryl-Monooleate Nanostructures Containing Paclitaxel

Abstract

Aims: This investigation compared the tumor distribution, efficacy, blood pharmacokinetic parameters and hematological alterations following treatment with chitosan/glyceryl-monooleate (GMO) nanostructures containing paclitaxel (PTX) to a conventional formulation of PTX (Taxol^®) in BALB/c female mice. Materials & methods: The tumor and blood concentrations of PTX were evaluated by HPLC and the pharmacokinetic parameters were determined through noncompartmental methods. Tumor development was evaluated by histopathological methods and hematological composition was monitored through differential white blood cells counts. Results: Lower localized or intravenous doses of PTX-chitosan/GMO nanostructures significantly increased the antitumor activity of paclitaxel. The tumor distribution studies showed effective concentrations in the tumors with the chitosan/GMO formulation while systemic blood levels remained lower than after administration of the conventional formulation. Conclusion: Delivery systems consisting of chitosan/GMO and PTX are safe and effective administered locally (intratumorally) or intravenously.

Keywords::

• blood pharmacokinetic parameters
• chitosan/glyceryl-monooleate nanostructures
• hematological alterations
• histopathological studies
• paclitaxel
• tumor distribution

Financial & competing interests disclosure

This work was partially supported by a Department of Defense Concept Award BC045664 and Health Future Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was partially supported by a Department of Defense Concept Award BC045664 and Health Future Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.