The effect of CTAB concentration in cationic PLG microparticles on DNA adsorption and in vivo performance.
OBJECTIVE
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.
Singh
Manmohan
M
Immunology and Infectious Diseases, Chiron Corporation 4560 Horton Street, Emeryville, California 94608, USA. manmohan_singh@chiron.com
Ugozzoli
Mildred
M
Briones
Maylene
M
Kazzaz
Jina
J
Soenawan
Elawati
E
O'Hagan
Derek T
DT
D000327:Adsorption / Q000187:drug effects; D000818:Animals; D002412:Cations; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D004247:DNA / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D019344:Lactic Acid / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*
D002412:Cations; D002593:Cetrimonium Compounds; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D004247:DNA; D000077286:Cetrimonium