Singh Manmohan, Fang Jia-Hwa, Kazzaz Jina, Ugozzoli Mildred, Chesko James, Malyala Padma, Dhaliwal Raj, Wei Rebecca, Hora Maninder, O'Hagan Derek
Novartis Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
Int J Pharm. 2006 Dec 11;327(1-2):1-5. doi: 10.1016/j.ijpharm.2006.07.033. Epub 2006 Jul 25.
We have previously shown that cationic polylactide-co-glycolide (PLG) microparticles can be effectively used to adsorb DNA and generate potent immune responses in vivo. We now describe a modified and easier process containing a single lyophilization step to prepare these cationic PLG microparticles with adsorbed DNA. Cationic PLG microparticle formulations with adsorbed DNA were prepared using a modified solvent evaporation technique. Formulations with a fixed CTAB content and DNA load were prepared. The loading efficiency and 24h DNA release was evaluated for each formulation and compared to the earlier method of preparation. Select formulations were tested in vivo. The modified cationic PLG microparticle preparation method with a single lyophilization step, showed comparable physico-chemical behaviour to the two lyophilization steps process and induced comparable immune. The modified process with a single lyophilization step is a more practical process and can be utlized to prepare cationic PLG microparticles with adsorbed DNA on a large scale.
我们之前已经表明，阳离子聚乳酸-羟基乙酸共聚物（PLG）微粒可有效地用于吸附DNA并在体内产生强烈的免疫反应。我们现在描述一种经过改进且更简便的方法，该方法包含一个冻干步骤，用于制备这些吸附了DNA的阳离子PLG微粒。采用改进的溶剂蒸发技术制备了吸附有DNA的阳离子PLG微粒制剂。制备了具有固定十六烷基三甲基溴化铵（CTAB）含量和DNA负载量的制剂。对每种制剂评估其负载效率和24小时DNA释放情况，并与早期的制备方法进行比较。选择的制剂进行了体内测试。具有单个冻干步骤的改进型阳离子PLG微粒制备方法，显示出与两个冻干步骤的方法具有相当的物理化学行为，并诱导产生了相当的免疫反应。具有单个冻干步骤的改进方法是一个更实用的方法，可用于大规模制备吸附有DNA的阳离子PLG微粒。
