Chitosan and chitosan ethylene oxide propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines
Chitosan and chitosan ethylene oxide propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines
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DOI：
10.1023/a:1012128907225
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发表时间：
1997-10-01
影响因子：
3.7
通讯作者：
Alonso, MJ
中科院分区：
文献类型：
--
作者：
Calvo, P;RemunanLopez, C;Alonso, MJ
目的。本研究的目的是研究新型壳聚糖(CS)与壳聚糖/环氧乙烷-环氧丙烷嵌段共聚物(PEO-PPO)纳米粒子之间的相互作用，并评价其对蛋白质和疫苗的缔合和控释作用。用X射线光电子能谱(XPS)分析了纳米粒子表面PEO-PPO的存在及其与壳聚糖的相互作用。用牛血清白蛋白(BSA)、破伤风类毒素和白喉类毒素等几种蛋白质，通过改变制备条件(不同的pH值和PEO-PPO的浓度)，以及蛋白质掺入纳米粒形成介质的阶段，阐明了蛋白质结合的机制。牛血清白蛋白、破伤风和白喉类毒素与CS纳米颗粒高度相关，部分原因是蛋白质的羧基和CS的胺基之间的静电相互作用。PEO-PPO还与CS以静电相互作用，从而与蛋白质竞争与CS纳米颗粒的结合。可见数量的PEO-PPO被投射到纳米颗粒的外相。蛋白质从纳米颗粒中以几乎恒定的速度释放，其强度与蛋白质的负载量密切相关。此外，破伤风疫苗以活性形式释放至少15天。通过非常温和的离子交联技术制备的CS和CS/PEO-PPO纳米颗粒是一种新型的适合于蛋白质和疫苗包埋和控制释放的体系。
Purpose. The aim of this study was to investigate the interaction between the components of novel chitosan (CS) and CS/ethylene oxide-propylene oxide block copolymer (PEO-PPO) nanoparticles and to evaluate their potential for the association and controlled release of proteins and vaccines.Methods. The presence of PEO-PPO on the surface of the nanoparticles and its interaction with the CS was identified by X-ray photoelectron spectroscopy (XPS). The mechanism of protein association was elucidated using several proteins, bovine serum albumin (BSA), and tetanus and diphtheria toxoids, and varying the formulation conditions (differ ent pH values and concentrations of PEO-PPO), and the stage of protein incorporation into the nanoparticles formation medium.Results. BSA and tetanus and diphtheria toxoids were highly associated with CS nanoparticles partly due to electrostatic interactions between the carboxyl groups of the protein and the amine groups of CS. PEO-PPO also interacted electrostatically with CS, thus competing with the proteins for association with CS nanoparticles. A visible amount of PEO-PPO was projected towards the outer phase of the nanoparticles. Proteins were released from the nanoparticles at an almost constant rate, the intensity of which was closely related to the protein loading. Furthermore, the tetanus vaccine was released in the active form for at least 15 days.Conclusions. CS and CS/PEO-PPO nanoparticles prepared by a very mild ionic crosslinking technique are novel and suitable systems for the entrapment and controlled release of proteins and vaccines.