Malyala Padma, Chesko James, Ugozzoli Mildred, Goodsell Amanda, Zhou Fengmin, Vajdy Michael, O'Hagan Derek T, Singh Manmohan
Novartis Vaccines and Diagnostics, 4560 Horton St., M/S 4.355, Emeryville, CA 94608, USA.
J Pharm Sci. 2008 Mar;97(3):1155-64. doi: 10.1002/jps.21065.
The objective of this work was to evaluate the potency of the CpG containing oligonucleotide encapsulated within poly(lactide-co-glycolide), and coadministered with antigen adsorbed to poly(lactide-co-glycolide) microparticles (PLG particles). The formulations evaluated include, CpG added in soluble form, CpG adsorbed, and CpG encapsulated. The antigen from Neisseria meningitidis serotype B (Men B) was used in these studies. The immunogenicity of these formulations was evaluated in mice. Poly(lactide-co-glycolide) microparticles were synthesized by a w/o/w emulsification method in the presence of a charged surfactant for the formulations. Neisseria meningitidis B protein was adsorbed to the PLG microparticles, with binding efficiency and initial release measured. CpG was either added in the soluble or adsorbed or encapsulated form based on the type of formulation. The binding efficiency, loading, integrity and initial release of CpG and the antigen were measured from all the formulations. The formulations were then tested in mice for their ability to elicit antibodies, bactericidal activity and T cell responses. Encapsulating CpG within PLG microparticles induced statistically significant higher antibody, bactericidal activity and T cell responses when compared to the traditional method of delivering CpG in the soluble form.
本研究的目的是评估包裹于聚（丙交酯-共-乙交酯）内并与吸附于聚（丙交酯-共-乙交酯）微粒（PLG微粒）上的抗原共同给药的含CpG寡核苷酸的效力。所评估的制剂包括以可溶形式添加的CpG、吸附的CpG和包裹的CpG。这些研究中使用了来自B型脑膜炎奈瑟菌（Men B）的抗原。在小鼠中评估了这些制剂的免疫原性。对于这些制剂，通过在带电表面活性剂存在下的w/o/w乳化法合成聚（丙交酯-共-乙交酯）微粒。将B型脑膜炎奈瑟菌蛋白吸附到PLG微粒上，并测定结合效率和初始释放量。根据制剂类型，以可溶、吸附或包裹形式添加CpG。测定所有制剂中CpG和抗原的结合效率、负载量、完整性和初始释放量。然后在小鼠中测试这些制剂引发抗体、杀菌活性和T细胞反应的能力。与以可溶形式递送CpG的传统方法相比，将CpG包裹于PLG微粒中可诱导统计学上显著更高的抗体、杀菌活性和T细胞反应。
