Comparison of nanoparticle uptake by cancer versus sites of inflammation
Development of a wide spectrum of targeted nanocarrier system promise to expand the therapeutic windows of drugs by increasing delivery to the target tissue versus the non-targeted counterpart. This will in turn lead to reduction in the minimum effective dose of the drug and an improvement in therapeutic efficacy at equivalent plasma concentrations. These involve the identification of precise targets such as cells and receptors related to specific conditions and choice of the appropriate nanocarriers to achieve the required responses while minimizing the side effects. Activated macrophages, which are abundant in inflamed tissues such as ulcerative colitis, rheumatoid arthritis, muscle injury and atherosclerosis were observed to over-express the folate receptor. Several inflammatory pathologies have been successfully imaged and quantified by FR-targeted small molecule imaging agents in both humans and animal models of human inflammatory diseases, demonstrating the specificity of FR in delivering drugs to sites of inflammation. FR-targeted small molecule therapeutic agents have also shown great promise for use in treating the same diseases, enabling suppression/elimination of the activated macrophages without collateral toxicity to healthy tissues. However, a majority of current folate linked imaging and therapeutic agents have been small molecules (< 1 KDa), thus leading to short circulating times in vivo (∼ 2 hour). Use of folate linked nanocarriers to target activated macrophages may prove very useful for the diagnosis and treatment of inflammatory diseases due to their longer circulation times and higher payloads. This has lead to the central objective of my research, which is to design a folate-linked nanocarrier that could target sites of inflammation. Although currently majority of the nanomedicine research focuses in the area of cancer. In this dissertation, two general areas of focus have been developed for the folate targeted nanocarriers: First, it is demonstrated that folate targeted nanocarriers such as liposomes and dendrimers can specifically target sites of inflammation via folate receptor. Folate targeted nanocarriers encapsulated with imaging agents and drugs show greater accumulation in the areas of inflammation than its non-targeted counterpart. Second, folate targeted liposome favors targeting sites of inflammation over solid tumors.
Low, Purdue University.
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