Fabrication and optimization of pH-sensitive mannose-anchored nano-vehicle as a promising approach for macrophage uptake

Mukhtar, Mehwish and Zeeshan, Mahira and Sarwar, Hafiz Shoaib Fabrication and optimization of pH-sensitive mannose-anchored nano-vehicle as a promising approach for macrophage uptake. Applied Nanosciences.

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Abstract

Mannose receptors (MR) are highly over-expressed on macrophages in the inflammatory bowel disease (IBD) and can be targeted by developing mannose-anchored nano-carrier system. In this study, mannosylated chitosan (MC) polymer was synthesized because of its high affinity for mannose receptors. Afterward, MC nanoparticles (NPs) were fabricated encapsulating dexamethasone to target macrophages for attenuation of inflammation at initial stages. Further, NPs were coated with a pH-sensitive polymer to control the premature drug release in the stomach. NPs were optimized using a surface response quadratic model to study the impact of various process parameters. Optimized NPs were then characterized for size, morphology, zeta potential, surface chemistry, biocompatibility, and uptake by macrophages. The average particle size was found to be 380 ± 19.8 nm with an encapsulation efficiency of 78.1 ± 1.17%. pH-dependent drug release profile was obtained with an average release of 73.9 ± 5.24% over 72 h in simulated intestinal fluid (pH 7.4). Moreover, the NPs uptake by the macrophages supported the viability of macrophages with the NPs and did not show any adverse effects. Moreover, this study was supported by the uptake of NPs inside macrophages. Altogether, the data supported that MC NPs could serve as a potential anti-inflammatory therapeutic approach to target macrophages in IBD.

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