Fabrication and optimization of pH-sensitive mannose-anchored nano-vehicle as a promising approach for macrophage uptake
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ORIGINAL ARTICLE
Fabrication and optimization of pH‑sensitive mannose‑anchored nano‑vehicle as a promising approach for macrophage uptake Mahwash Mukhtar1,2 · Mahira Zesshan1 · Salman Khan1 · Gul Shahnaz1 · Saeed Ahmad Khan3 · Hafiz Shoaib Sarwar1,4 · Riffat Asim Pasha5 · Hussain Ali1 Received: 24 April 2020 / Accepted: 8 July 2020 © King Abdulaziz City for Science and Technology 2020
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. Keywords Factorial design · Kinetics · Nanotechnology · Mannosylated chitosan · Polymer synthesis · Surface chemistry Abbreviations CD Crohn’s disease DEXA Dexamethasone DSC Differential scanning calorimetry EE Encapsulation efficiency Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13204-020-01510-y) contains supplementary material, which is available to authorized users. * Hussain Ali [email protected] 1
Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
2
Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös utca 6, Szeged 6720, Hungary
3
Department of Pharmacy, Kohat University of Science and Technology, Kohat 26000, Pakistan
4
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, Pakistan
5
Department of Mechanical Engineering, University of Engineering and Technology Taxila, Rawalpindi, Pakistan
ES100 Poly (methacrylic acid-co-methyl methacrylate) 1:2, Eudragit® S100 FBS Fetal bovine serum FTIR Fourier transform infrared spectroscopy GIT Gastrointestinal tract IBD Inflammatory bowel disease IRFs Interferons MC
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