pH-Responsive Alginate-Based Microparticles for Colon-Targeted Delivery of Pure Cyclosporine A Crystals to Treat Ulcerative Colitis

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.

Modulation of engineered nanomaterial interactions with organ barriers for enhanced drug transport

“…Alginate as an anionic linear polymer obtained from brown seaweed can be utilized in the formation of nanoparticles for GI tract delivery that may have probiotic benefits. 171,172 As alginate based vehicles have been found to respond to increasing pH levels by swelling in size, the design of any microcapsules should be considered. 173 Conversely, lipid nanoparticles (LNPs) have been found to have stable release profiles within a large range of pH values which would allow for the delivery through the GI tract.…”

“…Alginate as an anionic linear polymer obtained from brown seaweed can be utilized in the formation of nanoparticles for GI tract delivery that may have probiotic benefits. 171,172 As alginate based vehicles have been found to respond to increasing pH levels by swelling in size, the design of any microcapsules should be considered. 173…”

Mucoadhesive Nanoparticles Enhance the Therapeutic Effect of Dexamethasone on Experimental Ulcerative Colitis by the Local Administration as an Enema

“…It is also a widely used natural polymer material for medicine due to its low toxicity, good biocompatibility, and degradability. 31 , 32 The excellent mucosal adhesion of SA makes it attach to the mucosa through the interaction between the molecular chain and mucin and increase the viscosity of mucus. 33 In this study, to realize the adhesion to the positively charged inflammatory colonic mucosa, the PEI-DDs NPs were further self-assembled with SA to build the final bilayer complex NPs, SA-PEI-DDs ( Scheme 1 ).…”

Cyclosporine A-Encapsulated pH/ROS Dual-Responsive Nanoformulations for the Targeted Treatment of Colitis in Mice

“…To decrease the adverse effects of therapeutics, several smart responsive nanoplatforms were developed to deliver therapeutics for the targeted treatment of colitis. For example, glutathione-, pH- or thermoresponsive nanoplatforms were used to load methotrexate, cyclosporine A (CsA), , recombinant human lactoferrin, and procyanidin for alleviation of colitis, respectively. In addition, pH/ROS and pH/glutathione dual responsive delivery systems were also employed to deliver astaxanthin, curcumin, and ginsenoside for the targeted treatment of IBD.…”