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用于 IgA 抗体靶向口服递释的肠溶性聚合物包覆多孔硅纳米粒子。

Enteric Polymer-Coated Porous Silicon Nanoparticles for Site-Specific Oral Delivery of IgA Antibody.

机构信息

Department of Chemistry and Biochemistry, University of California, San Diego, California 92093, United States.

School of Materials Science and Engineering, University of New South Wales-Sydney, Sydney, NSW 2052, Australia.

出版信息

ACS Biomater Sci Eng. 2022 Oct 10;8(10):4140-4152. doi: 10.1021/acsbiomaterials.0c01313. Epub 2020 Nov 20.

Abstract

Porous silicon (pSi) nanoparticles are loaded with Immunoglobulin A-2 (IgA2) antibodies, and the assembly is coated with pH-responsive polymers on the basis of the Eudragit family of enteric polymers (L100, S100, and L30-D55). The temporal release of the protein from the nanocomposite formulations is quantified following an protocol simulating oral delivery: incubation in simulated gastric fluid (SGF; at pH 1.2) for 2 h, followed by a fasting state simulated intestinal fluid (FasSIF; at pH 6.8) or phosphate buffer solution (PBS; at pH 7.4). The nanocomposite formulations display a negligible release in SGF, while more than 50% of the loaded IgA2 is released in solutions at a pH of 6.8 (FasSIF) or 7.4 (PBS). Between 21 and 44% of the released IgA2 retains its functional activity. A capsule-based system is also evaluated, where the IgA2-loaded particles are packed into a gelatin capsule and the capsule is coated with either EudragitL100 or EudragitS100 polymer for a targeted release in the small intestine or the colon, respectively. The capsule-based formulations outperform polymer-coated nanoparticles , preserving 45-54% of the activity of the released protein.

摘要

多孔硅 (pSi) 纳米粒子负载免疫球蛋白 A2 (IgA2) 抗体,并基于肠聚合物 Eudragit 家族 (L100、S100 和 L30-D55) 在其表面涂覆 pH 响应性聚合物。根据模拟口服给药的方案定量测定蛋白质从纳米复合制剂中的释放情况:在模拟胃液 (SGF; pH 1.2) 中孵育 2 h,然后在禁食状态下模拟肠液 (FasSIF; pH 6.8) 或磷酸盐缓冲液 (PBS; pH 7.4) 中孵育。纳米复合制剂在 SGF 中几乎没有释放,而在 pH 为 6.8 (FasSIF) 或 7.4 (PBS) 的溶液中,超过 50%的负载 IgA2 被释放。释放的 IgA2 中约有 21%至 44%保留其功能活性。还评估了基于胶囊的系统,其中将负载 IgA2 的颗粒装入明胶胶囊中,并将胶囊分别用 EudragitL100 或 EudragitS100 聚合物包衣,以在小肠或结肠中进行靶向释放。基于胶囊的制剂优于聚合物包衣的纳米颗粒,可保留释放蛋白质 45%-54%的活性。

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