Delivery of rapamycin to dendritic cells using degradable microparticles

JOURNAL OF CONTROLLED RELEASE

卷:133

Article

Jhunjhunwala, S.^1,6  Raimondi, G.^2,5  Thomson, A. W.^2,3,5  Little, S. R.^1,3,4,6 

[1] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA

[2] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15260 USA

[3] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15260 USA

[4] Univ Pittsburgh, Dept Chem Engn, Pittsburgh, PA 15260 USA

[5] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15260 USA

[6] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15260 USA

关键词: Microparticles;    PLGA;    Rapamycin;    Dendritic cells;    Intracellular delivery;   

DOI  :  10.1016/j.jconrel.2008.10.011

来源: Elsevier

【 摘 要 】

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 similar to 3.4 mu m 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. (C) 2008 Elsevier B.V. All rights reserved.

【 授权许可】

Free