Tafaghodi Mohsen, Jaafari Mahmood-Reza, Sajadi Tabassi Sayyed Abolghasem
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Eur J Pharm Biopharm. 2006 Oct;64(2):138-45. doi: 10.1016/j.ejpb.2006.05.005. Epub 2006 May 20.
To increase the systemic and mucosal immune responses against the nasally administered tetanus toxoid, liposomes as a drug delivery system and CpG-ODN as an adjuvant were evaluated. Rabbits were nasally immunized with entrapped tetanus toxoid (TT) and CpG-ODN in neutral liposomes and systemic and mucosal immune responses were determined. Liposomes containing TT and CpG-ODN were prepared by dehydration-rehydration method. The volume mean diameter of liposomes was 2.3+/-0.6 microm. Encapsulation efficiency of TT and CpG-ODN was determined as 54.0+/-8.8 and 60.1+/-7.4, respectively. The leakage of the encapsulated TT from liposomes reached 7.38% after 3 months. Encapsulated TT kept its intact structure, and its immunoreactivity was also completely preserved, as shown by SDS-PAGE and ELISA methods. The highest serum IgG and antitoxin titers were observed in groups immunized with solution formulations (P < 0.001). However the highest mucosal sIgA titers were achieved by liposomes encapsulated with TT. CpG-ODN as an adjuvant was able to increase the serum IgG and antitoxin titers when co-administered with TT solution (P < 0.05) or co-encapsulated with TT in liposomes (P < 0.01), but failed to increase the sIgA titers in nasal lavages. No hemolysis occurred on incubation of liposomes and human RBCs. Also after nasal administration of plain liposomes to human volunteers, no local irritation was seen. Intranasal administration of liposomes encapsulated with vaccines showed to be an effective way for inducing the mucosal immune responses.
为增强针对经鼻接种破伤风类毒素的全身和黏膜免疫反应，对作为药物递送系统的脂质体和作为佐剂的CpG-寡脱氧核苷酸（CpG-ODN）进行了评估。用包封于中性脂质体中的破伤风类毒素（TT）和CpG-ODN经鼻免疫家兔，并测定全身和黏膜免疫反应。采用脱水-复水法制备含TT和CpG-ODN的脂质体。脂质体的体积平均直径为2.3±0.6微米。TT和CpG-ODN的包封率分别测定为54.0±8.8和60.1±7.4。3个月后，脂质体中包封的TT泄漏率达7.38%。如SDS-PAGE和ELISA方法所示，包封的TT保持其完整结构，其免疫反应性也完全得以保留。在用溶液制剂免疫的组中观察到最高的血清IgG和抗毒素滴度（P<0.001）。然而，TT包封的脂质体实现了最高的黏膜分泌型IgA（sIgA）滴度。当与TT溶液共同给药（P<0.05）或与TT共同包封于脂质体中（P<0.01）时，作为佐剂的CpG-ODN能够提高血清IgG和抗毒素滴度，但未能提高鼻腔灌洗液中的sIgA滴度。脂质体与人红细胞孵育时未发生溶血。同样，向人类志愿者经鼻给予空白脂质体后，未观察到局部刺激。经鼻给予疫苗包封的脂质体显示是诱导黏膜免疫反应的有效途径。
