Abstract
Cyclosporine A (CsA) is a potent immunosuppressant for treating ulcerative colitis (UC). However, owing to severe systemic side effects, CsA application in UC therapy remains limited. Herein, a colon-targeted drug delivery system consisting of CsA crystals (CsAc)-loaded, Eudragit S 100 (ES)-coated alginate microparticles (CsAc-EAMPs) was established to minimize systemic side effects and enhance the therapeutic efficacy of CsA. Homogeneously-sized CsAs (3.1 ± 0.9 μm) were prepared by anti-solvent precipitation, followed by the fabrication of 47.1 ± 6.5 μm-sized CsAc-EAMPs via ionic gelation and ES coating. CsAc-EAMPs exhibited a high drug loading capacity (48 ± 5%) and a CsA encapsulation efficacy of 77 ± 9%. The in vitro drug release study revealed that CsA release from CsAc-EAMPs was suppressed under conditions simulating the stomach and small intestine, resulting in minimized systemic absorption and side effects. Following exposure to the simulated colon conditions, along with ES dissolution and disintegration of alginate microparticles, CsA was released from CsAc-EAMPs, exhibiting a sustained-release profile for up to 24 h after administration. Given the effective colonic delivery of CsA molecules, CsAc-EAMPs conferred enhanced anti-inflammatory activity in mouse model of dextran sulfate sodium (DSS)-induced colitis. These findings suggest that CsAc-EAMPs is a promising drug delivery system for treating UC.
Highlights
Published: 6 September 2021Ulcerative colitis (UC) is a chronic, relapsing disease of the gastrointestinal tract (GIT)that causes inflammation and ulcers in the mucosal lining of the colon and rectum [1].This multifactorial disease is associated with dysregulated expression of multiple genes in combination with microbial and environmental factors
Given the effective colonic delivery of cyclosporine A (CsA) molecules, CsA crystals (CsAc)-EAMPs conferred enhanced anti-inflammatory activity in mouse model of dextran sulfate sodium (DSS)-induced colitis. These findings suggest that CsAc-EAMPs is a promising drug delivery system for treating ulcerative colitis (UC)
E-cadherin expression in the colonic epithelium. These results indicated that CsAc-EAMPs administration could prompt barrier function recovery in the colon via effective modulation of colitis
Summary
That causes inflammation and ulcers in the mucosal lining of the colon and rectum [1] This multifactorial disease is associated with dysregulated expression of multiple genes in combination with microbial and environmental factors. Cyclosporine A (CsA), a peptide produced by the fermentation by aerobic fungi such as Aspergillus terreus and Tolypocladium inflatum, is widely employed as an immunosuppressant owing to its potent anti-inflammatory effects [6]. It exerts its anti-inflammatory activity via inhibiting interleukin-2 production in activated T-lymphocytes through a calcineurin-dependent pathway, thereby alleviating inflammation [7].
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