Enhancing the Efficacy of Chemotherapeutic Breast Cancer Treatment with Nonanticoagulant Heparins
Abstract
Studies with mice bearing MCF7-WT xenografts demonstrate that encapsulation of Dox, whether in targeted or non-targeted PLGA nanoparticles, improved anti-tumor efficacy in comparison to un-encapsulated Dox. In animals bearing MCF7-R (Dox-resistant) tumors, administration of Dox encapsulated in av 3-targeted nanoparticles or of Dox with nonanticoagulant heparin (NACH) are potent strategies for overcoming Dox resistance in animals bearing these aggressive human breast tumors. HPLC analyses of tumors and tissues from animals bearing MCF7-R tumors clearly demonstrate that LMWH or NACH increase the uptake of Dox into tumors but not other tissues at 3 and 24 hrs, at least double the amount observed with Dox alone. This is a highly significant result in the light of the fact that the FDA criterion for a clinically meaningful effect is a 15% increase in chemotherapeutic uptake. In vitro studies to investigate possible mechanisms associated with LMWH improvement of Dox anti-tumor activity focused on cell migration, proliferation and viability. LMWH compounds did not substantially affect these parameters in vitro. It is likely that increasing chemotherapeutic uptake in vivo as demonstrated in HPLC studies represents one important mechanism of improved anti-tumor efficacy associated with co-administration of LMWH and Dox.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2010
- Accession Number
- ADA587642
Entities
People
- Patricia G. Phillips
- Shaker A. Mousa
Organizations
- Albany College of Pharmacy and Health Sciences