A biomimetic orally targeted delivery of Bindarit for immunotherapy of atherosclerosis
Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the development of atherosclerosis. However, the application of bindarit (a specific synthetic inhibitor of MCP-1) in atherosclerosis has not been confirmed due to the non-specific distribution profile in vivo. Herein, based on the recruitment of monocytes to atherosclerotics plaques, we successfully delivered bindarit into the interior of atherosclerotic plaque through a yeast-derived microcapsule (YC) mediated biomimetic approach. In this biomimetic approach, bindarit was firstly assembled with polyethyleneimine to form positvely charged nanoparticles (BIN/PEI NPs) via multiple intermolecular force, and then the obtained BIN/PEI NPs were packed into YCs though electrostatic forces-mediated spontaneous deposition. Through an oral adsorption routine similar to yeasts, bindarit loaded YCs (BIN/YCs) were distributed into peripheral blood monocytes after oral administration, and then successfully targeted delivered to atherosclerotic plaques through the monocytes transportation. Correspondingly, oral delivery of bindarit loaded YCs afforded notably potentiated efficacies for inhibiting the MCP-1 and further reducing the monocytes recruitment to atherosclerotic plaque, thus presented a good efficacy in preventing the formation of atherosclerotic plaques. These results demonstrated that ‘Trojan horse’-like YC mediated nanomedicinal delivery strategy is expected to realize the application of certain potential anti-inflammatory drugs in the treatment of atherosclerosis and is of great significance for the development of novel strategies for atherosclerosis treatment.