期刊
JOURNAL OF CONTROLLED RELEASE
卷 262, 期 -, 页码 151-158出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.07.034
关键词
PCL-PEG; PCL-PEI; Delivery system; Nasal vaccine
资金
- National Natural Science Foundation of China [81422044, 81673362]
Increasing attention has been paid to nasal delivery. Subunit vaccines based on antigenic proteins or polypeptides offer good safety. However, lack of delivery efficiency, particularly for nasal immunization, is a big issue. Here we designed a highly tunable polymeric hybrid micelle (PHM) system offering good vaccine efficacy after nasal administration. PHMs are formulated from two amphiphilic diblock copolymers, polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG), the ratio of which determines PHM physicochemical properties. Citraconic anhydride-modified ovalbumin (Cit-OVA), as model antigen, was incorporated into PHMs via electrostatic interaction, giving antigen-loaded micelles of around 150 nm in size. Their surface characteristics which are found closely related to their in vivo kinetics can be modulated by adjusting the mass ratio of PCL-PEG and PCL-PEI. PHM/Cit-OVA complexes containing PCL-PEI and PCL-PEG in a 1: 1 mass ratio induced strong immune responses in nasal mucosa and serum in vivo without causing obvious toxicity, and Cit-OVA was efficiently internalized by dendritic cells. These results demonstrate the promise of this multifunctional polymeric delivery system for nasal vaccination.
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