Quillaja saponaria extract as mucosal adjuvant with chitosan functionalized gold nanoparticles for mucosal vaccine delivery: Stability and immunoefficiency studies
Quillaja saponaria extract as mucosal adjuvant with chitosan functionalized gold nanoparticles for mucosal vaccine delivery: Stability and immunoefficiency studies
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DOI：
10.1016/j.ijpharm.2012.10.033
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发表时间：
2013-01-30
影响因子：
5.8
通讯作者：
Pokharkar, Varsha
中科院分区：
文献类型：
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作者：
Barhate, Ganesh;Gautam, Manish;Pokharkar, Varsha
载体介导的疫苗沿着佐剂的递送可能解决与口服疫苗相关的问题，如免疫增强不足。在这项研究中，壳聚糖功能化的金纳米粒子（CsAuNPs）被用作载体的模型抗原破伤风类毒素（TT）沿着与免疫刺激剂皂树提取物（QS）。研究了制剂的理化性质（粒度、zeta电位、pH值）作为稳定性指示参数。合成的CsAuNP为球形，大小约40 nm，带正电荷（约+35 mV），TT和QS有效载荷分别为65%和0.01%。通过FTIR、荧光和CD光谱法测定，处方参数未改变TT的二级结构。通过ELISA测定的抗原特异性也未受损。CsAuNPs在体外研究中赋予TT抗胃水解的保护作用。在BALB/c小鼠中口服施用制剂后，与对照制剂（TT、TT-QS）相比，TT-QS-CsAuNP诱导高达28倍的免疫应答。通过使用ELISA测量TT特异性IgG和伊加滴度来定量免疫应答。本文的发现表明，TT和QS与功能化CsAuNP的共递送促进更好的全身和局部免疫应答，因此可以被认为是口服疫苗递送的合理方法。(C)2012 Elsevier B. V.保留所有权利。
Carrier mediated delivery of vaccines along with adjuvants can possibly address the issue related to oral vaccines like inadequate immune potentiation. In this study, chitosan functionalized gold nanoparticles (CsAuNPs) were used as a carrier for the model antigen tetanus toxoid (TT) along with immunostimulant Quillaja saponaria extract (QS). Physicochemical properties (size, zeta potential, pH value) of formulation were investigated as stability indicating parameters. The synthesized CsAuNPs were spherical in shape, around 40 nm in size, positively charged (around +35 mV) and had TT and QS payload of 65% and 0.01%, respectively. Formulation parameters did not alter the secondary structure of TT, as determined by FTIR, fluorescence and CD spectroscopy. Antigen specificity, determined by an ELISA, was also not compromised. The CsAuNPs conferred protection to TT against gastric hydrolysis as studied in vitro. TT-QS-CsAuNPs induced up to 28-fold immune responses compared to control formulations (TT, TT-QS) after oral administration of formulations in BALB/c mice. The immune responses were quantified by measuring the TT-specific IgG and IgA titers using ELISA. Findings herein demonstrate that co-delivery of TT and QS with functionalized CsAuNPs promotes better systemic and local immune responses and hence can be considered as a sound approach for oral vaccine delivery. (C) 2012 Elsevier B.V. All rights reserved.