A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides.
A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides.
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DOI：
10.2147/ijn.s116063
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发表时间：
2017
影响因子：
8
通讯作者：
Rafiee Tehrani M
中科院分区：
文献类型：
--
作者：
Barbari GR;Dorkoosh FA;Amini M;Sharifzadeh M;Atyabi F;Balalaie S;Rafiee Tehrani N;Rafiee Tehrani M
报道了一种简单且可重复的油包水（W/O）纳米乳液技术，用于从壳聚糖（CS）制备超小（<15 nm）、单分散和水分散性纳米粒（NPs）。W/O纳米乳液的纳米尺寸（50 nm）水池充当“纳米容器和纳米反应器”。这些“纳米反应器”内的CS的截留聚合物链与聚乙二醇（PEG）的链共价交联，导致硬化和形成NP。这些NP在水性介质中具有过度溶胀性质，并且由于与PEG的化学交联而在所有pH范围内保持完整性。一个有效的和新开发的细胞穿透肽（CPP）进一步化学共轭的NP的表面，导致开发一种新的肽共轭衍生物的CS具有深刻的紧密连接开放性能。CPP缀合的纳米颗粒可以容易地负载几乎所有种类的蛋白质、肽和核苷酸用于口服递送应用。在Caco-2细胞系中研究了该纳米颗粒系统用于口服递送模型肽（胰岛素）的可行性。胰岛素跨细胞单层易位的细胞培养结果非常有希望（增加15%-19%），动物研究正在积极进行中，将单独发表。
A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O nanoemulsion serve as “nano-containers and nano-reactors”. The entrapped polymer chains of CS inside these “nano-reactors” are covalently cross-linked with the chains of polyethylene glycol (PEG), leading to rigidification and formation of NPs. These NPs possess excessive swelling properties in aqueous medium and preserve integrity in all pH ranges due to chemical cross-linking with PEG. A potent and newly developed cell-penetrating peptide (CPP) is further chemically conjugated to the surface of the NPs, leading to development of a novel peptide-conjugated derivative of CS with profound tight-junction opening properties. The CPP-conjugated NPs can easily be loaded with almost all kinds of proteins, peptides and nucleotides for oral delivery applications. Feasibility of this nanoparticulate system for oral delivery of a model peptide (insulin) is investigated in Caco-2 cell line. The cell culture results for translocation of insulin across the cell monolayer are very promising (15%–19% increase), and animal studies are actively under progress and will be published separately.