科研之友
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摘要
A poly(amidoamine) with disulfide linkages in the main chain and 4-hydroxybutyl and -carboxy-PEG groups (9:1 ratio) as side chains was prepared by Michael addition polymerization of cystamine bisacrylamide with 4-hydroxybutylamine and -carboxy-PEG-amine. To develop therapeutic protein formulations for improved delivery of antigen via the intranasal route, nanoparticles were prepared from this polymer by self-assembly with p24 or ovalbumin as the model proteins and CpG as the adjuvant. The nanoparticles incorporated the antigens and adjuvant from the feed solution with high efficiency (approximate to 90%) and have sizes of 112 and 169nm, respectively, with low positive surface charge (approximate to+2mV). Formulations of the nanoparticles were shown to be nontoxic and stable for at least 10 days at room temperature. Their capacity to pass through epithelial and endothelial cell layers was evaluated in vitro by using a respiratory mucosa-like barrier model in which monolayers of NCIH441 respiratory epithelial cells and ISO-HAS-1 endothelial cells were co-cultured on both sides of a transwell filter membrane. It was shown that p24 incorporated in the nanoparticles was transported with %26gt;140% greater efficiency through the two contact-inhibited layers than p24 in its free form, whereas incorporation of ovalbumin in the nanoparticles leads to a 40% decrease in transport efficiency relative to the free antigen.
- 出版日期2013-11
