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

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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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Abbreviations

CD:

Crohn’s disease

DEXA:

Dexamethasone

DSC:

Differential scanning calorimetry

EE:

Encapsulation efficiency

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:

Mannosylated chitosan

MR:

Mannose receptor

NF-κB:

Nuclear factor-kappa activated B cells

NPs:

Nanoparticles

PAF:

Platelet activating factor

PAMPs:

Pathogen-associated molecular patterns

PDI:

Polydispersity index

PRRs:

Pattern recognition receptors

Rh-B:

Rhomadine B

SEM:

Scanning electron microscope

SGF:

Simulated gastric fluid

SIF:

Simulated intestinal fluid

TC:

Thiolated chitosan

TGA:

Thioglycolic acid

UC:

Ulcerative colitis

XPS:

X-ray photon spectroscopy

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Mahwash Mukhtar, Mahira Zesshan, Salman Khan, Gul Shahnaz, Hafiz Shoaib Sarwar & Hussain Ali

  2. Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös utca 6, Szeged, 6720, Hungary

    Mahwash Mukhtar

  3. Department of Pharmacy, Kohat University of Science and Technology, Kohat, 26000, Pakistan

    Saeed Ahmad Khan

  4. Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, Pakistan

    Hafiz Shoaib Sarwar

  5. Department of Mechanical Engineering, University of Engineering and Technology Taxila, Rawalpindi, Pakistan

    Riffat Asim Pasha

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  1. Mahwash Mukhtar
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  2. Mahira Zesshan
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  3. Salman Khan
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  4. Gul Shahnaz
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  8. Hussain Ali
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Mukhtar, M., Zesshan, M., Khan, S. et al. Fabrication and optimization of pH-sensitive mannose-anchored nano-vehicle as a promising approach for macrophage uptake. Appl Nanosci 10, 4013–4027 (2020). https://doi.org/10.1007/s13204-020-01510-y

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  • DOI: https://doi.org/10.1007/s13204-020-01510-y

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