Boonyo Worawan, Junginger Hans E, Waranuch Neti, Polnok Assadang, Pitaksuteepong Tasana
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
J Control Release. 2007 Aug 28;121(3):168-75. doi: 10.1016/j.jconrel.2007.05.025. Epub 2007 Jun 2.
Chitosan of different molecular weights (Chi-P, MW=2.7x10(5) g/mol and Chi-A, MW=5.0x10(5) g/mol) and trimethyl chitosan chloride (TMC) of various degree of quaternization (DQ) including TMC-20, TMC-40 and TMC-60 were evaluated as adjuvants for inducing of immune responses to ovalbumin (OVA). OVA in solution and in alum were used as controls. Groups of BALB/c mice were immunized on days 0, 7 and 14. The IgG and IgA titers were examined on days 0, 13 and 21. It was found that for both days 13 and 21, Chi-A could elicit higher IgG responses to OVA than Chi-P. On day 13, OVA in TMC-40 induced IgG responses significantly higher than that in solution, Chi-P and TMC-60. Moreover, OVA in TMC-40 could induce IgG responses higher than OVA in alum. Although a significant difference was not observed at day 21, OVA in TMC-40 was shown to induce higher IgG responses than that in TMC-20, TMC-60 and solution. The IgA responses were the most pronounced on day 21. Again, Chi-A could elicite higher IgA responses than Chi-P and TMC-40 induced the highest IgA responses. In conclusion, these findings demonstrate that both MW of chitosan and DQ of TMC influence the level of immune induction. TMC-40 shows to be the most potent adjuvant for intranasal administration.
对不同分子量的壳聚糖(Chi-P,分子量 = 2.7×10⁵ g/mol和Chi-A,分子量 = 5.0×10⁵ g/mol)以及不同季铵化程度(DQ)的氯化三甲基壳聚糖(TMC)(包括TMC-20、TMC-40和TMC-60)作为诱导对卵清蛋白(OVA)免疫反应的佐剂进行了评估。溶液中的OVA和明矾中的OVA用作对照。BALB/c小鼠组在第0、7和14天进行免疫。在第0、13和21天检测IgG和IgA滴度。结果发现,在第13天和第21天,Chi-A对OVA引发的IgG反应均高于Chi-P。在第13天,TMC-40中的OVA诱导的IgG反应显著高于溶液、Chi-P和TMC-60中的OVA。此外,TMC-40中的OVA诱导的IgG反应高于明矾中的OVA。尽管在第21天未观察到显著差异,但TMC-40中的OVA诱导的IgG反应高于TMC-20、TMC-60和溶液中的OVA。IgA反应在第21天最为明显。同样,Chi-A引发的IgA反应高于Chi-P,TMC-40诱导的IgA反应最高。总之,这些发现表明壳聚糖的分子量和TMC的季铵化程度均影响免疫诱导水平。TMC-40被证明是鼻内给药最有效的佐剂。