Chitosan and chitosan ethylene oxide propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines

被引:634
作者
Calvo, P [1 ]
RemunanLopez, C [1 ]
VilaJato, JL [1 ]
Alonso, MJ [1 ]
机构
[1] UNIV SANTIAGO DE COMPOSTELA,SCH PHARM,DEPT PHARM & PHARMACEUT TECHNOL,SANTIAGO COMPOSTE 15706,SPAIN
关键词
chitosan; ethylene oxide propylene oxide block copolymer; nanoparticles; vaccine delivery; protein delivery; ionic gelation;
D O I
10.1023/A:1012128907225
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:1431 / 1436
页数:6
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