4.6 Article

Alginate-Based Oral Delivery Systems to Enhance Protection, Release, and Absorption of Catalase

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ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 9, 期 6, 页码 3390-3401

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AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.3c00278

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oral drug delivery; catalase; therapeutic proteins; alginate; polygalacturonic acid; pectin; M cells

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Oxidative stress and overproduction of reactive oxygen species (ROS) play a crucial role in the development of inflammatory bowel diseases. Catalase, which can scavenge hydrogen peroxide (one of the ROS produced in cellular metabolism), has great therapeutic potential. However, its in vivo application for ROS scavenging, especially through oral administration, is currently limited. This study introduced an alginate-based oral drug delivery system that effectively protected catalase from the harsh conditions of the gastrointestinal tract, released it in a pH-dependent manner, and enhanced its absorption via specialized epithelial cells in the small intestine.
Oxidative stress, overproduction of reactive oxygen species(ROS),plays an important role in the development of inflammatory bowel diseases.Catalase has great therapeutic potential by scavenging hydrogen peroxide,one of the ROSs produced in cellular metabolisms. However, in vivoapplication to scavenge ROS is currently limited especially in oraladministrations. Here, we introduced an alginate-based oral drug deliverysystem that effectively protected catalase from the simulated harshconditions of the gastrointestinal (GI) tract, released it in thesmall intestine mimicked condition, and enhanced its absorption viaM cells, highly specialized epithelium cells in the small intestine.First of all, catalase was encapsulated in alginate-based microparticleswith different amounts of polygalacturonic acid or pectin, which achievedan encapsulation efficiency of more than 90%. It was further shownthat catalase was released from alginate-based microparticles in apH-dependent manner. Results indicated that alginate-polygalacturonicacid microparticles (60 wt % Alg:40 wt % Gal) released 79.5 +/- 2.4% of encapsulated catalase at pH 9.1 in 3 h, while they only released9.2 +/- 1.5% of encapsulated catalase at pH 2.0. Even when catalasewas encapsulated in microparticles (60 wt % Alg:40 wt % Gal) and exposedto pH 2.0 followed by pH 9.1, it still retained 81.0 +/- 11.3%enzyme activity compared to that in microparticles prior to the pHtreatment. We then investigated the efficiency of RGD conjugationto catalase on the catalase uptake by M-like cells, the coculturingof human epithelial colorectal adenocarcinoma; Caco-2 cells and Blymphocyte; Raji cells. RGD-catalase protected M-cells more efficientlyfrom the cytotoxicity of H2O2, a typical ROS.RGD conjugation to catalase enhanced the uptake by M-cells with 87.6 +/- 0.8% RGD-catalase, whereas 11.5 +/- 9.2% of RGD-free catalasepassed across M-cells. From the results of protection, release, andabsorption of model therapeutic proteins from the harsh pH conditions,alginate-based oral drug delivery systems will have numerous applicationsfor the controlled release of drugs that are easily degradable inthe GI tract.

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