期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 11, 期 5, 页码 1039-1046出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2015.02.021
关键词
Atherosclerosis; Nanomedicine; Glucocorticoids; Macrophages
资金
- European Framework Program 7 grant [FP7-Health 309820]
- Dutch network for Nanotechnology NanoNext NL, in the subprogram Drug Delivery
- National Heart, Lung, and Blood Institute, National Institutes of Health, as a Program of Excellence in Nanotechnology (PEN) Award [HHSN268201000045C]
- NIH [R01 HL118440, R01 HL125703, R01 EB009638]
- NWO Vidi [91713324]
- Enceladus Pharmaceuticals (Amsterdam, The Netherlands)
- International Atherosclerosis Society (USA)
- Foundation De Drie Lichten (The Netherlands)
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. From the Clinical Editor: In this study, the authors undertook the first clinical trial using long-circulating liposomal nanoparticle encapsulating prednisolone in patients with atherosclerosis, based on previous animal studies. Despite little evidence of anti-inflammatory effect, the results have provided a starting point for future development of nanomedicine in cardiovascular diseases.(C) 2015 Elsevier Inc. All rights reserved.
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