BackgroundColon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer.MethodsCSA-loaded Eudragit FS30D nanoparticles (ENPs), PLGA nanoparticles (PNPs), and Eudragit FS30D/PLGA nanoparticles (E/PNPs) were prepared using the oil-in-water emulsion method. Scanning electron microscope images and zeta size data showed successful preparation of CSA-loaded NPs.ResultsPNPs exhibited a burst drug release of >60% at pH 1.2 (stomach pH) in 0.5 h, which can lead to unwanted systemic absorption and side effects. ENPs effectively inhibited the burst drug release at pH 1.2 and 6.8 (proximal small intestine pH); however, nearly 100% of the CSA in ENPs was released rapidly at pH 7.4 (ileum–colon pH) owing to complete NP dissolution. In contrast to single-functional PNPs and ENPs, the dual-functional E/PNPs minimized burst drug release (only 18%) at pH 1.2 and 6.8, and generated a sustained release at pH 7.4 thereafter. Importantly, in distribution studies in the gastrointestinal tracts of mice, E/PNPs significantly improved CSA distribution to the colon compared with PNPs or ENPs. In a mouse model of colitis, E/PNP treatment improved weight loss and colon length, and decreased rectal bleeding, spleen weight, histological scoring, myeloperoxidase activity, macrophage infiltration, and expression of proinflammatory cytokines compared with PNPs or ENPs.ConclusionOverall, this work confirms the benefits of CSA-loaded E/PNPs for efficiently delivering CSA to the colon, suggesting their potential for UC therapy.

Adhesion of nanoparticles (NPs) to the bacterial cell wall by modifying their physicochemical properties can improve the antibacterial activity of antibiotic. In this study, we prepared positively charged clindamycin-loaded poly (lactic-co-glycolic acid)-polyethylenimine (PLGA-PEI) nanoparticles (Cly/PPNPs) and negatively charged clindamycin-loaded PLGA NPs (Cly/PNPs) and investigated the effect of NP adhesion to bacteria on the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The Cly/PPNPs and Cly/PNPs were characterized according to particle size, polydispersity index, surface charge, and drug loading. Both Cly/PPNPs and Cly/PNPs exhibited sustained drug release over 2 days. The Cly/PPNPs bind to the MRSA surface, thereby enhancing bactericidal efficacy against MRSA compared with the Cly/PNPs. Furthermore, compared with other groups, Cly/PPNPs significantly accelerated the healing and re-epithelialization of wounds in a mouse model of a MRSA-infected wounds. We also found that both NPs are harmless to healthy fibroblast cells. Therefore, our results suggest that the Cly/PPNPs developed in this study improve the efficacy of clindamycin for the treatment of MRSA-infected wounds.

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.

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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.