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Targeting of Macrophages in Inflammation With Thermosensitive Biopolymers

Immune cells such as pro-inflammatory folate receptor positive (FR+) activated macrophages play a key role in the development of inflammatory diseases . Because treatment of most inflammation pathologies are encumbered by unwanted side effects that arise from the deposition of drug into wrong tissues . The logical remedy for these undesirable properties involves selective targeting of the therapeutic agent to pathologic cells, thereby avoiding collateral toxic ity to healthy cells and undesirable side effects. Previous published work has demonstrated that activated macrophages overexpress folate receptor (but not resting macrophages) that can be exploited for selective targeting and internalization of small molecular folate conjugates (SMFCs) (Mw < 3000) proven useful in sites of inflammation in both human patients and animal models, however little work has been investigated on nanoscale drug delivery system such as biopolymer nanoparticle. Although, peptide drugs may be effective in promoting anti-inflammatory effects but poor bioavailability limits its commercial application, thereby alternative delivery approaches must be sought. In recent years, temperature sensitive polymeric nanoparticles have attracted much attention for their potential biomedical applications in delivering drug to tumor sites and inflamed tissues. For this purpose, we propose designing a nanoscale drug carrier that function as selective targeting and ability to protect peptide drug from enzymatic degradation, thus increasing the half-life of the peptide for diagnostics and therapeutic treatment. By combining folate-targeting and biopolymer as a carrier, we examined whether folate-targeted thermosensit ive polymer (FTSP) loaded with fluorescent and therapeutic cargos could selectively target folate receptor positive (FR+) activated macrophages, presenting the opportunity to both visualize and suppressing pro-inflammatory mediators, with little or no collateral toxicity to healthy cells.