Plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B
Plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B
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DOI：
10.1016/j.ijpharm.2007.11.027
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发表时间：
2008-04-16
影响因子：
5.8
通讯作者：
Vyas, Suresh P.
中科院分区：
文献类型：
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作者：
Khatri, Kapil;Goyal, Amit K.;Vyas, Suresh P.
本工作研究了载质粒DNA壳聚糖纳米粒的制备及其在鼻黏膜免疫中的体内效果。对所制备的纳米粒子的大小、形状、表面电荷、载质粒、保护DNA免受核酸酶消化的能力以及它们的转染效率进行了表征。纳米粒鼻腔给药后，小鼠血清中的抗-HBs滴度低于裸露DNA和明矾吸附的HBs-Ag，但在2周内达到血清保护性水平，免疫球蛋白水平高于临床保护性水平。然而，肌肉注射裸露的DNA和吸附了乙肝表面抗原的明矾并不能诱导由壳聚糖纳米颗粒鼻腔免疫所诱导的粘膜分泌物中的SLGA滴度。同样，在明矾吸附了乙肝表面抗原的情况下，细胞反应(细胞因子水平)很差。因此，壳聚糖纳米粒在鼻腔给药后产生体液(包括全身和粘膜)和细胞免疫反应。本研究表明壳聚糖纳米粒作为DNA疫苗载体和佐剂具有通过非侵入性鼻腔途径进行有效免疫的潜力。(C)2007 Elsevier B.V.保留所有权利。
This work investigates the preparation and in vivo efficacy of plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B. Chitosan pDNA nanoparticles were prepared using a complex coacervation process. Prepared nanoparticles were characterized for size, shape, surface charge, plasmid loading and ability of nanoparticles to protect DNA against nuclease digestion and for their transfection efficacy. Nasal administration of nanoparticles resulted in serum anti-HBsAg titre that was less compared to that elicited by naked DNA and alum adsorbed HBsAg, but the mice were seroprotective within 2 weeks and the immunoglobulin level was above the clinically protective level. However, intramuscular administration of naked DNA and alum adsorbed HBsAg did not elicit slgA titre in mucosal secretions that was induced by nasal immunization with chitosan nanoparticles. Similarly, cellular responses (cytokine levels) were poor in case of alum adsorbed HBsAg. Chitosan nanoparticles thus produced humoral (both systemic and mucosal) and cellular immune responses upon nasal administration. The study signifies the potential of chitosan nanoparticles as DNA vaccine carrier and adjuvant for effective immunization through non-invasive nasal route. (C) 2007 Elsevier B.V. All rights reserved.