Our laboratory is also examining novel approaches to drug delivery in inflammatory and neoplastic conditions. Cancer is the second leading cause for death in the United States, exceeded by heart disease. Tumor metastasis and recurrence are major causes of death, and many tumors rapidly develop resistance to chemotherapeutic agents. Therefore we are interested in novel methods of drug delivery using nanotechnology. Such methods can be used to target specific tumors based on predominant antigens on the tumor vasculature.
Drug Delivery to Tumor Vessels
The process of reproduction, development, and repair of cells fundamentally depends on antiogenesis. Tumor cells in the early phase of growth can absorb nutrients and oxygen from surrounding tissue and develop up to 1-3 mm in an avascular condition, in this phase usually they are clinically undetectable; but for further growth they should be vascularized. Neovascularization is stimulated with a diffusible material that is released by tumor cells. These vessels have abnormal morphological characteristics. Therefore, tumor vessels can be targeted to prevent angiogenesis and/or deliver drugs into neoplastic cells distant from tumor vessels. One advantage of vascular targeting is that tumor endothelium is genetically more stable than tumor cells, so that drug resistance is uncommon.
Long Circulating Biodegradable Nanoparticle
We currently target tumor endothelium using a biodegradable polymer particle containing chemotherapeutic agents. This particle can be conjugated with antibodies to provide specificity. Encapsulation of active molecules in nanoparticles is one of the promising ways for optimizing the therapeutic effect and decreasing systemic toxicity. We have attempted to increase the circulation time of nanoparticles by decreasing the size of particles, and modifying the nanoparticle composition. Large particles are rapidly removed by the liver and spleen in comparison to smaller particles. We are currently performing in-vivo testing of this approach.
