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壳聚糖-苯丙氨酸-甲氧基聚乙二醇纳米颗粒:从一步水基共轭到潜在的过敏原递送系统。

Chitosan-phenylalanine-mPEG nanoparticles: From a single step water-based conjugation to the potential allergen delivery system.

作者信息

Jirawutthiwongchai Jatesuda, Klaharn I-Yanut, Hobang Nattapat, Mai-Ngam Katanchalee, Klaewsongkram Jettanong, Sereemaspun Amornpun, Chirachanchai Suwabun

机构信息

The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok 10330, Thailand.

Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10300, Thailand.

出版信息

Carbohydr Polym. 2016 May 5;141:41-53. doi: 10.1016/j.carbpol.2015.12.076. Epub 2015 Dec 31.

Abstract

The chemical modification to obtain biocompatible chitosan (CS) nanoparticles for the application in biological system is still on expectation. By simply mixing CS with hydroxybenzotriazole (HOBt), the CS aqueous solution obtained allows a successful single step conjugation of both hydrophobic biomolecules, i.e. phenylalanine (Phe), and hydrophilic polymers, i.e. poly(ethylene glycol) methyl ether (mPEG), on CS, in water at room temperature. The CS-Phe-mPEG nanoparticles (20-50nm) exhibit positive charge leading to an entrapment of negatively charged house dust mite allergen (HDM) extract (Dermatophagoides pteronyssinus). The HDM-entrapped CS-Phe-mPEG shows biocompatibility as evidenced from the cell viability, the ROS (reactive oxygen species) reduction, and the HaCaTs proliferation. The clinical implementation on the healthy- and HDM-allergic volunteers indicates that the HDM-entrapped CS-Phe-mPEG stimulates cell-mediated immune response in peripheral blood mononuclear cells (PBMCs) and favors T cell immune response as seen from the reduction of interferon-(IFN)-γ and interleukin-(IL)-10 in the PBMCs of the HDM-allergic volunteers.

摘要

为在生物系统中应用而获得生物相容性壳聚糖(CS)纳米颗粒的化学修饰仍备受期待。通过简单地将CS与羟基苯并三唑(HOBt)混合,所得的CS水溶液能够在室温下于水中成功地将疏水性生物分子(即苯丙氨酸(Phe))和亲水性聚合物(即聚乙二醇甲醚(mPEG))在CS上进行单步共轭。CS-Phe-mPEG纳米颗粒(20 - 50nm)带正电荷,导致能够包载带负电荷的屋尘螨变应原(HDM)提取物(粉尘螨)。包载HDM的CS-Phe-mPEG表现出生物相容性,这从细胞活力、活性氧(ROS)减少以及HaCaTs增殖得到证明。对健康和HDM过敏志愿者的临床实施表明,包载HDM的CS-Phe-mPEG刺激外周血单个核细胞(PBMC)中的细胞介导免疫反应,并有利于T细胞免疫反应,这从HDM过敏志愿者的PBMC中干扰素 -(IFN)-γ和白细胞介素 -(IL)-10的减少可以看出。

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