The importance of the problem of cancer is shown by the report which indicates that more than 1.3 million cases of cancer are diagnosed annually and that cancer claims an estimated 570,280 lives in the United States each year. It is believed that cancer is second only to cardiovascular diseases as a cause of mortality among Americans. The most common cancers in United States are prostate, breast, lung and colorectal cancers. Thus cancer does not discriminate on the basis of gender. Both extrinsic factors [e.g., tobacco smoking, chemicals, drugs, hormones, radiations (such as ionizing radiations and ultraviolet light), and infections (such as viral infections)] and patient intrinsic factors (e.g., inherited metabolism mutations, hormones, and immune conditions) are believed to be important initiators of cancers. Frantic efforts have been made over the years to identify factors affecting successful treatment of cancer: tumor burden, tumor-cell heterogeneity, drug resistance, dose intensity, and poor selectivity of the drug. Moreover, a great deal of research has been carried out to find ways and means to circumvent the problems of cancer treatment: targeted delivery of drugs to cancer, in vivo detection of cancer biomarkers, detection of cancer biomarkers ex vivo, overcoming biological barriers to the biophase (site of action), identification of potential targets and targeting moieties for anti-cancer drug delivery systems, drug combination, and the development of efficient drug carriers. There is a need for the integration of all these efforts. The development of multifunctional polymeric nanospheres for cancer therapy, which is the long-term objective of this application, could make the integration possible. The core of the nanosphere can be loaded with anti-cancer agents, imaging agent, and agents to overcome pump and non-pump resistance;targeting moieties and agents responsive to biomarkers could be tagged to the external coating made of poly(ethylene glycol). All these will achieve early detection of cancer and provide effective killing of the cancer cells. The goal of the research in this application is to initiate efforts that will make it possible to achieve the capabilities of multifunctional nanoparticles by developing paclitaxel-loaded stealth nanospheres based on biocompatible and biodegradable poly(lactic acid). Synthesis of biodegradable and biocompatible macromonomers, fabrication and characterization of paclitaxel-loaded nanopsheres and their evaluation for cell uptake and cytotoxicity in the BT-20 human breast carcinoma cell line are the focus of this proposal.
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|Adesina, Simeon K; Holly, Alesia; Kramer-Marek, Gabriela et al. (2014) Polylactide-based paclitaxel-loaded nanoparticles fabricated by dispersion polymerization: characterization, evaluation in cancer cell lines, and preliminary biodistribution studies. J Pharm Sci 103:2546-55|