Curcumin Nanocrystal/pH-Responsive Polyelectrolyte Multilayer Core–Shell Nanoparticles for Inflammation-Targeted Alleviation of Ulcerative Colitis

Abstract

In this study, we developed oral core−shell nanoparticles composed of curcumin nanocrystals in the core and chitosan/alginate multilayers in the shell for inflammation-targeted alleviation of ulcerative colitis (UC). The release rate of curcumin from the core−shell nanoparticles was low at a pH mimicking the stomach and small intestine, whereas it was higher at a pH mimicking the colon. Further, biodistribution studies in the gastrointestinal tract of mice showed that distribution of nanoparticles was significantly higher in the colon than that in the stomach and small intestine. Quantitative analysis of drugs in colonic tissues and confocal imaging of colons revealed preferential accumulation of nanoparticles in inflamed tissues than that in healthy tissues. In vivo antiinflammatory studies revealed that nanoparticles exhibit enhanced efficacy in alleviating inflammation-related symptoms in a mouse colitis model. The results suggest that the core−shell nanoparticles presented here can be exploited as efficient colon-targeted drug delivery systems for UC therapy.

Curcumin and Its Modified Formulations on Inflammatory Bowel Disease (IBD): The Story So Far and Future Outlook

“…CAP1AG4CH5@CUNCs feature the pH-dependent release of curcumin and high colonic distribution in mice in in vitro and biodistribution studies. Eventually, CAP1AG4CH5@CUNCs exhibited a better therapeutic potential in treating DSS-induced colitis in mice and were acknowledged as an excellent system to deliver drugs in the colon for UC treatment [119]. Luo et al [120] synthesized a nanocarrier having a tannic acid (TA)-coated genipin (GNP)-crosslinked human serum albumin (HSA) to encapsulate curcumin and prepared curcumin nanoparticles (TA/CUR-NPs).…”

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

“…The animal study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of Pusan National University Institutional Animal Care and Use Committee (protocol code PNU-2019-2420 on 23 October 2019). DSS-induced colitis was induced in mice using a previously reported method with some modifications [ 19 ]. Briefly, ICR mice (male, 6-week-old) were obtained from Samtako Bio Korea (Osan, Korea).…”

“…In this regard, pure drug crystals with a particle diameter ˂10 μm could be a promising drug delivery system to overcome these limitations [ 17 , 18 ]. Unlike polymeric nano- and microparticles, pure drug crystals can deliver an extremely high amount of drugs to the colon owing to their high loading capacity (~100%) [ 19 ]. In addition, pure drug crystals could benefit from the enhanced permeability effect induced by inflammation and accumulate in inflamed colonic regions [ 20 , 21 ].…”

Recent Progress in the Diagnosis and Precise Nanocarrier-Mediated Therapy of Inflammatory Bowel Disease

“… 89 Because the IBD lesions are concentrated in the ileum and colon, 20 specific pH-mediated stimulated drug delivery platforms are being developed as options for controlled drug release. Stealth materials such as hydroxypropyl methylcellulose acetate succinate (HPMCAS) polymers, 90 , 91 hydrogels 92 and Eudragit S 100 93 are widely used to design pH-responsive DDSs with core-shell structures, nano-in-micro structures, and hierarchical structures. Some of the solid studies are depicted below.…”

“… 96 For example, Oshi et al designed and synthesized a hydrogel (chitosan/alginate)-based pH-triggered activatable core-shell nanoparticle (CAP 1 AG 4 CH 5 @CUNC) by using ultrasound-assisted antisolvent crystallization and LBL-coating techniques for use in drug delivery for IBD therapy. 92 The core-shell structure system is composed of an inner curcumin nanocrystals (CUNC) core surrounded by chitosan (CH), sodium alginate (AG), and cellulose acetate phthalate (CAP). Due to the insoluble properties of CAP in the gastric pH, the system remained intact in the upper GIT.…”