School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
J Drug Target. 2010 Apr;18(3):235-42. doi: 10.3109/10611860903434035.
The immunoadjuvant potential of alginate microspheres as delivery system, and cross-linked dextran microspheres (CDM) as absorption enhancer and excipient for powder of alginate microspheres, were evaluated. Alginate microspheres were prepared by emulsification method. Microspheres encapsulated with tetanus toxoid (TT) or Quillaja saponin (QS) were nasally administered to rabbits, three times in 2 weeks interval and serum IgG and nasal lavage sIgA titers were determined by ELISA. The mean diameter of microspheres was about 1.5 mum. Release of TT and QS was 13.1 +/- 1.4% and 31.8 +/- 4.3% after 4 h. The serum IgG titer induced with (TT)(ALG) microspheres was higher than TT solution (P<0.001). Addition of QS or CDM adjuvant, in separate, to (TT)(ALG) microspheres could not significantly increase the immune responses (P>0.05), but the highest systemic IgG titers induced with (TT+QS)(ALG)+CDM (P<0.01). The sIgA titer induced with (TT)(ALG) microspheres was higher than TT solution (P<0.05). The highest mucosal sIgA titers were seen in animals immunized with (TT)(ALG)+CDM (P<0.05). Co-encapsulation of QS and TT in microspheres did not increase the sIgA titers. When CDM was added to alginate microspheres encapsulated with TT or TT+QS, the highest mucosal and systemic responses were observed.
研究了海藻酸钠微球作为给药系统的免疫佐剂潜力，以及交联葡聚糖微球（CDM）作为海藻酸钠微球粉末的吸收增强剂和赋形剂。采用乳化法制备海藻酸钠微球。将破伤风类毒素（TT）或 Quillaja saponin（QS）包封的微球经鼻腔给予家兔，每 2 周 3 次，通过 ELISA 测定血清 IgG 和鼻洗液 sIgA 滴度。微球的平均直径约为 1.5 µm。TT 和 QS 的释放量分别为 4 小时后 13.1±1.4%和 31.8±4.3%。（TT）（ALG）微球诱导的血清 IgG 滴度高于 TT 溶液（P<0.001）。分别向（TT）（ALG）微球中添加 QS 或 CDM 佐剂，不能显著增加免疫反应（P>0.05），但（TT+QS）（ALG）+CDM 诱导的最高全身 IgG 滴度（P<0.01）。（TT）（ALG）微球诱导的 sIgA 滴度高于 TT 溶液（P<0.05）。在免疫接种（TT）（ALG）+CDM 的动物中观察到最高的粘膜 sIgA 滴度（P<0.05）。QS 和 TT 共包封在微球中不会增加 sIgA 滴度。当 CDM 被添加到包封 TT 或 TT+QS 的海藻酸钠微球中时，观察到最高的粘膜和全身反应。
