Jung T, Kamm W, Breitenbach A, Hungerer K D, Hundt E, Kissel T
Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany.
Pharm Res. 2001 Mar;18(3):352-60. doi: 10.1023/a:1011063232257.
Aim of the study was the evaluation of the potential of novel tetanus toxoid (TT) loaded nanoparticles (NP) for electing an immune response in mice against TT.
Six week-old female Balb/c mice were immunized by oral (p.o.), nasal (i.n.) and intraperitoneal (i.p.) application of TT NP loaded by adsorption. As polymer a novel polyester, sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide), SB(43)-PVAL-g-PLGA was used. Blood samples were collected 4 and 6 weeks after immunization and assayed for serum IgG- as well as IgA antibody titers by ELISA. NP formulations varying in size and loading were compared to alum adsorbates as well as to TT solutions.
Both, p.o. and i.n. administration of TT associated NP increased serum titers up to 3 x 10(3) (IgG) and 2 x 10(3) (IgA). While small NP induced significantly higher titers then larger ones after oral administration, intermediate NP induced antibodies after nasal application. Of the mucosal routes investigated, i.n. seems to be more promising compared to p.o. immunization.
Antigen loaded NP prepared from surface modified polyesters combined with CT show considerable potential as a vaccine delivery system for mucosal immunization. The results warrant further experiments to explore in more detail the potential use of NP as mucosal vaccine delivery system.
本研究旨在评估新型负载破伤风类毒素（TT）的纳米颗粒（NP）在小鼠体内引发针对TT的免疫反应的潜力。
六周龄雌性Balb/c小鼠通过口服（p.o.）、鼻腔（i.n.）和腹腔内（i.p.）应用吸附负载TT的NP进行免疫。作为聚合物，使用了一种新型聚酯，磺丁基化聚乙烯醇接枝聚（丙交酯-共-乙交酯），SB(43)-PVAL-g-PLGA。在免疫后4周和6周采集血样，并通过ELISA测定血清IgG和IgA抗体滴度。将不同大小和负载量的NP制剂与明矾吸附物以及TT溶液进行比较。
口服和鼻腔给予与TT相关的NP均可使血清滴度分别提高至3×10³（IgG）和2×10³（IgA）。口服给药后，小尺寸NP诱导的滴度显著高于大尺寸NP，而鼻腔给药后中等尺寸NP诱导产生抗体。在所研究的黏膜途径中，与口服免疫相比，鼻腔免疫似乎更具前景。
由表面改性聚酯与CT组合制备的负载抗原的NP作为黏膜免疫的疫苗递送系统具有相当大的潜力。这些结果值得进一步实验，以更详细地探索NP作为黏膜疫苗递送系统的潜在用途。
