TY - JOUR
T1 - Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration
AU - van der Valk, Fleur M.
AU - van Wijk, Diederik F.
AU - Lobatto, Mark E.
AU - Verberne, Hein J.
AU - Storm, Gert
AU - Willems, Martine C.M.
AU - Legemate, Dink A.
AU - Nederveen, Aart J.
AU - Calcagno, Claudia
AU - Mani, Venkatesh
AU - Ramachandran, Sarayu
AU - Paridaans, Maarten P.M.
AU - Otten, Maarten J.
AU - Dallinga-Thie, Geesje M.
AU - Fayad, Zahi A.
AU - Nieuwdorp, Max
AU - Schulte, Dominik M.
AU - Metselaar, Josbert M.
AU - Mulder, Willem J.M.
AU - Stroes, Erik S.G.
PY - 2015
Y1 - 2015
N2 - Drug delivery to atherosclerotic plaques via liposomal nanoparticles may improve therapeutic agents’ risk–benefit ratios. Our paper details the first clinical studies of a liposomal nanoparticle encapsulating prednisolone (LN-PLP) in atherosclerosis. First, PLP’s liposomal encapsulation improved its pharmacokinetic profile in humans (n = 13) as attested by an increased plasma half-life of 63 h (LN-PLP 1.5 mg/kg). Second, intravenously infused LN-PLP appeared in 75% of the macrophages isolated from iliofemoral plaques of patients (n = 14) referred for vascular surgery in a randomized, placebo-controlled trial. LN-PLP treatment did however not reduce arterial wall permeability or inflammation in patients with atherosclerotic disease (n = 30), as assessed by multimodal imaging in a subsequent randomized, placebo-controlled study. In conclusion, we successfully delivered a long-circulating nanoparticle to atherosclerotic plaque macrophages in patients, whereas prednisolone accumulation in atherosclerotic lesions had no anti-inflammatory effect. Nonetheless, the present study provides guidance for development and imaging-assisted evaluation of future nanomedicine in atherosclerosis.
AB - Drug delivery to atherosclerotic plaques via liposomal nanoparticles may improve therapeutic agents’ risk–benefit ratios. Our paper details the first clinical studies of a liposomal nanoparticle encapsulating prednisolone (LN-PLP) in atherosclerosis. First, PLP’s liposomal encapsulation improved its pharmacokinetic profile in humans (n = 13) as attested by an increased plasma half-life of 63 h (LN-PLP 1.5 mg/kg). Second, intravenously infused LN-PLP appeared in 75% of the macrophages isolated from iliofemoral plaques of patients (n = 14) referred for vascular surgery in a randomized, placebo-controlled trial. LN-PLP treatment did however not reduce arterial wall permeability or inflammation in patients with atherosclerotic disease (n = 30), as assessed by multimodal imaging in a subsequent randomized, placebo-controlled study. In conclusion, we successfully delivered a long-circulating nanoparticle to atherosclerotic plaque macrophages in patients, whereas prednisolone accumulation in atherosclerotic lesions had no anti-inflammatory effect. Nonetheless, the present study provides guidance for development and imaging-assisted evaluation of future nanomedicine in atherosclerosis.
KW - 2024 OA procedure
U2 - 10.1016/j.nano.2015.02.021
DO - 10.1016/j.nano.2015.02.021
M3 - Article
SN - 1743-5889
VL - 11
SP - 1039
EP - 1046
JO - Nanomedicine
JF - Nanomedicine
IS - 5
ER -
