TY - JOUR
T1 - Delivery of rapamycin to dendritic cells using degradable microparticles
AU - Jhunjhunwala, S.
AU - Raimondi, G.
AU - Thomson, A. W.
AU - Little, S. R.
N1 - Funding Information:
We thank Marc Rubin for assistance with the SEM, Jennifer Karlsson, Catherine Baty and Simon Watkins for help with the differential interference contrast microscopy. This work was supported by NIH grants AI 67541, AI 60994, KL2 RR024154-02 and the American Heart Association grant 0730081N. GR is in receipt of a research fellowship from the Transplantation Society.
PY - 2009/2/10
Y1 - 2009/2/10
N2 - Degradable microparticles have the potential to protect and release drugs over extended periods and, if sized appropriately, can be passively targeted to phagocytic cells in vivo. Dendritic cells (DC) are a class of phagocytic cells known to play important roles in transplant rejection. Previously, we have demonstrated that DC treated with an immunosuppressive drug, rapamycin, have the ability to suppress transplant rejection. Herein, we describe a strategy to deliver an intracellular depot of rapamycin to DC. To achieve this, rapamycin was encapsulated into ~ 3.4 μm sized poly(lactic-co-glycolic)acid (PLGA) microparticles (rapaMPs), and release behavior was examined under intra-phagosomal (pH = 5) and extracellular (pH = 7.4) conditions. It was observed that 4 days following phagocytosis of rapaMP, DC have significantly reduced ability to activate T cells, in comparison to DC treated with soluble rapamycin. Hence, we conclude that DC-specific intracellular delivery of rapamycin results in better efficacy of the drug, with respect to its ability to modulate DC function, when compared to treating DC with extracellular rapamycin.
AB - Degradable microparticles have the potential to protect and release drugs over extended periods and, if sized appropriately, can be passively targeted to phagocytic cells in vivo. Dendritic cells (DC) are a class of phagocytic cells known to play important roles in transplant rejection. Previously, we have demonstrated that DC treated with an immunosuppressive drug, rapamycin, have the ability to suppress transplant rejection. Herein, we describe a strategy to deliver an intracellular depot of rapamycin to DC. To achieve this, rapamycin was encapsulated into ~ 3.4 μm sized poly(lactic-co-glycolic)acid (PLGA) microparticles (rapaMPs), and release behavior was examined under intra-phagosomal (pH = 5) and extracellular (pH = 7.4) conditions. It was observed that 4 days following phagocytosis of rapaMP, DC have significantly reduced ability to activate T cells, in comparison to DC treated with soluble rapamycin. Hence, we conclude that DC-specific intracellular delivery of rapamycin results in better efficacy of the drug, with respect to its ability to modulate DC function, when compared to treating DC with extracellular rapamycin.
KW - Dendritic cells
KW - Intracellular delivery
KW - Microparticles
KW - PLGA
KW - Rapamycin
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U2 - 10.1016/j.jconrel.2008.10.011
DO - 10.1016/j.jconrel.2008.10.011
M3 - Article
C2 - 19000726
AN - SCOPUS:58549112593
SN - 0168-3659
VL - 133
SP - 191
EP - 197
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -