Dual pH and microbial-sensitive galactosylated polymeric nanocargoes for multi-level targeting to combat ulcerative colitis

Mahira Zeeshan; Qurat Ul Ain; Benno Weigmann; Darren Story; Bryan R Smith; Hussain Ali

doi:10.1016/j.ajps.2023.100831

Dual pH and microbial-sensitive galactosylated polymeric nanocargoes for multi-level targeting to combat ulcerative colitis

Asian J Pharm Sci. 2023 Jul;18(4):100831. doi: 10.1016/j.ajps.2023.100831. Epub 2023 Jul 26.

Authors

Mahira Zeeshan^{1

2

3}, Qurat Ul Ain¹, Benno Weigmann², Darren Story^{4

5}, Bryan R Smith^{4

5}, Hussain Ali¹

Affiliations

¹ Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
² Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen 91052, Germany.
³ Faculty of Pharmacy, Capital University of Science and Technology, Islamabad 44000, Pakistan.
⁴ Biomedical Engineering Department, Michigan State University, East Lansing 48824, USA.
⁵ Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing 48824, USA.

Abstract

Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by inflammation, ulcers and irritation of the mucosal lining. Oral drug delivery in UC encounters challenges because of multifaceted barriers. Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes (Dexa-GP/ES/Pu NCs) have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota, and an underneath galactosylated-PLGA core (GP). The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C (MGL-2) surface receptor. Therefore, both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake. Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs. The nanocargoes were tested using in vitro, ex vivo techniques and dextran sodium sulfate (DSS) induced UC model. Prepared nanocargoes had desired physicochemical properties, drug release, cell uptake and cellular viability. Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2, and restoration of clinical, histopathological, biochemical indices, antioxidant balance, microbial alterations, FTIR spectra, and epithelial junctions' integrity. Thus, Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.

Keywords: Galactosylated nanocargoes; Macrophage galactose type-lectin C; Microbial sensitive; Pullulan; Ulcerative colitis; pH-sensitive drug delivery.