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The Effect of CTAB Concentration in Cationic PLG Microparticles on DNA Adsorption and in Vivo Performance
Authors:Singh  Manmohan  Ugozzoli  Mildred  Briones  Maylene  Kazzaz  Jina  Soenawan  Elawati  O'Hagan  Derek T
Institution:(1) Immunology and Infectious Diseases, Chiron Corporation, 4560 Horton Street, Emeryville, California, 94608;(2) Immunology and Infectious Diseases, Chiron Corporation, 4560 Horton Street, Emeryville, California, 94608
Abstract:Purpose. Cationic PLG microparticles with adsorbed DNA have previously been shown to efficiently target antigen presenting cells in vivo for generating higher immune responses in comparison to naked DNA. In this study we tried to establish the role of surfactant (CTAB) concentration on the physical behavior of these formulations. Methods. Cationic PLG microparticle formulations with adsorbed DNA were prepared using a solvent evaporation technique. Formulations with varying CTAB concentrations and a fixed DNA load were prepared. The loading efficiency and 24 h DNA release was evaluated for each formulation. Select formulations were tested in vivo. Results. Higher CTAB concentration correlated with higher DNA binding efficiency on the microparticles and lower in vitro release rates. Surprisingly though, the in vivo performance of formulations with varying CTAB concentration was comparable to one another. Conclusions. Cationic PLG microparticles with adsorbed DNA, as described here, offer a robust way of enhancing in vivo responses to plasmid DNA.
Keywords:CTAB  cationic microparticles  PLG (polylactide-co-lycolide)  DNA delivery  adjuvant  vaccines
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