A modified process for preparing cationic polylactide-co-glycolide microparticles with adsorbed DNA

A modified process for preparing cationic polylactide-co-glycolide microparticles with adsorbed DNA
Received 13 June 2006; revised 18 July 2006; accepted 19 July 2006. Available online 25 July 2006.
Manmohan Singh, a, , Jia-Hwa Fanga, Jina Kazzaza, Mildred Ugozzolia, James Cheskoa, Padma Malyalaa, Raj Dhaliwala, Rebecca Weia, Maninder Horaa and Derek O?Hagana
International Journal of Pharmaceutics
Volume 327, Issues 1-2 , 11 December 2006
ScienceDirect
Copyright ? 2006 Elsevier B.V. All rights reserved.
aNovartis Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA
Abstract
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 24 h 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.
Keywords: PLG microparticles; Lyophilization; Double emulsion; Cationic surface
Abbreviations: TE, Tris?EDTA buffer; SDS, sodium dodecyl sulphate; CTAB, cetyltrimethylammonium bromide; PLG, polylactide-co-glycolide; LYO, lyophilization

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