TY - JOUR
T1 - Targeted delivery of immunomodulating agents to dendritic cells for treatment of autoimmune disease using biodegradable microspheres
AU - Brunner, Tali
AU - Monsonego, Alan
AU - Cohen, Smadar
PY - 2007
Y1 - 2007
N2 - Dendritic cells (DCs) are a central elementfor drug targeting in autoimmune diseases, due to theirfunction in the onset and progression of destructiveautoimmunity and in maintaining the Treg repertoire.When injected intradermally, microspheres sized 1–10microns are preferentially uptaken by DCs. Use of suchmicrospheres has been investigated for delivery of antigensand DNA to DCs for vaccination; however this deliverysystem has not been implemented for delivery of siRNAscapable of regulating autoimmunity.In vivodelivery ofsiRNA is a great challenge, since these RNA duplexes arerapidly degraded and require appropriate stabilization.Goal: To use biodegradable microspheres for deliveringsiRNA and other immunomodulating agents to DCs, fortreatment of autoimmune disease. Results: Microspherescomposed of poly-lactic-acid better target CD11c positivecells in a bone marrow DC (BMDC) culture, in comparison toa poly-lactic-co-glycolic composition. siRNA, stabilizedusing poly-ethylene-imine and encapsulated in micro-spheres using a double-emulsion procedure, remainedactive after release from microspheres in BMDCs. Impor-tantly, the microspheres did not have an adjuvant effectupon the BMDCs compared with LPS-induced DC-mediatedT cell proliferation, meaning that the BMDCs maintainedtheir immature state, which is crucial for creating animmunoregulatory environment which can ameliorate thecourse of autoimmune disease
AB - Dendritic cells (DCs) are a central elementfor drug targeting in autoimmune diseases, due to theirfunction in the onset and progression of destructiveautoimmunity and in maintaining the Treg repertoire.When injected intradermally, microspheres sized 1–10microns are preferentially uptaken by DCs. Use of suchmicrospheres has been investigated for delivery of antigensand DNA to DCs for vaccination; however this deliverysystem has not been implemented for delivery of siRNAscapable of regulating autoimmunity.In vivodelivery ofsiRNA is a great challenge, since these RNA duplexes arerapidly degraded and require appropriate stabilization.Goal: To use biodegradable microspheres for deliveringsiRNA and other immunomodulating agents to DCs, fortreatment of autoimmune disease. Results: Microspherescomposed of poly-lactic-acid better target CD11c positivecells in a bone marrow DC (BMDC) culture, in comparison toa poly-lactic-co-glycolic composition. siRNA, stabilizedusing poly-ethylene-imine and encapsulated in micro-spheres using a double-emulsion procedure, remainedactive after release from microspheres in BMDCs. Impor-tantly, the microspheres did not have an adjuvant effectupon the BMDCs compared with LPS-induced DC-mediatedT cell proliferation, meaning that the BMDCs maintainedtheir immature state, which is crucial for creating animmunoregulatory environment which can ameliorate thecourse of autoimmune disease
U2 - 10.1016/j.clim.2007.03.051
DO - 10.1016/j.clim.2007.03.051
M3 - תקציר הצגה בכנס
SN - 1521-6616
VL - 123
SP - S145-S146
JO - Clinical Immunology
JF - Clinical Immunology
ER -
