Targeted chelation therapy with EDTA-loaded albumin nanoparticles regresses arterial calcification without causing systemic side effects.
Targeted chelation therapy with EDTA-loaded albumin nanoparticles regresses arterial calcification without causing systemic side effects.
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DOI：
10.1016/j.jconrel.2014.09.029
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发表时间：
2014-12-28
期刊：
影响因子：
--
通讯作者：
Vyavahare N
中科院分区：
文献类型：
--
作者：
Lei Y;Nosoudi N;Vyavahare N
弹性蛋白特异性内侧动脉钙化(MAC)是一种通常被称为蒙克伯格硬化症的动脉疾病。它会导致显著的动脉僵硬，但到目前为止，还没有临床治疗方法来预防或逆转它。我们开发了负载乙二胺四乙酸二钠(EDTA)的白蛋白纳米粒(NPs)，用于在静脉注射时靶向钙化的弹性板层。优化了纳米粒的大小、电荷和载药效率(15 0~2 0 0 nm，zeta电位−2 2.89~−31.72 mV，载药效率2 0%~2 0%)。这些NPs缓慢释放EDTA长达5天。在体外和体内对损伤诱导的局部腹主动脉钙化的研究中，我们发现弹性蛋白抗体包裹和EDTA负载的白蛋白纳米粒靶向受损的弹力板，而保留健康的动脉。静脉注射NP逆转了大鼠在两周内四次注射后的弹性蛋白特异性MAC。载EDTA的白蛋白纳米粒不会引起单独注射EDTA的副作用，如血钙降低、尿钙升高或对肾脏的毒性。所有治疗组均未见骨丢失。我们证明，弹性蛋白抗体包裹和EDTA负载的白蛋白纳米粒可能是一种有前途的纳米颗粒疗法，可以逆转弹性蛋白特异性MAC并避免与全身EDTA螯合治疗相关的副作用。
Elastin-specific medial arterial calcification (MAC) is an arterial disease commonly referred as Monckeberg’s sclerosis. It causes significant arterial stiffness, and as yet, no clinical therapy exists to prevent or reverse it. We developed albumin nanoparticles (NPs) loaded with disodium ethylene diaminetetraacetic acid (EDTA) that were designed to target calcified elastic lamina when administrated by intravenous injection. We optimized NP size, charge, and EDTA-loading efficiency (150~200 nm, zeta potential of − 22.89 ~ − 31.72 mV, loading efficiency for EDTA ~20 %) for in vivo targeting in rats. These NPs released EDTA slowly for up to 5 days. In both ex-vivo study and in vivo study with injury-induced local abdominal aortic calcification, we showed that elastin antibody-coated and EDTA-loaded albumin NPs targeted the damaged elastic lamina while sparing healthy artery. Intravenous NP injections reversed elastin-specific MAC in rats after four injections over a 2-week period. EDTA-loaded albumin NPs did not cause the side effects observed in EDTA injection alone, such as decrease in serum calcium (Ca), increase in urine Ca, or toxicity to kidney. There was no bone loss in any treated groups. We demonstrate that elastin antibody-coated and EDTA-loaded albumin NPs might be a promising nanoparticle therapy to reverse elastin-specific MAC and circumvent side effects associated with systemic EDTA chelation therapy.
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DOI：
10.1016/0735-1097(95)00206-j
发表时间：
1995-09-01
影响因子：
24
作者：
MACISAAC, AI;BASS, TA;WHITLOW, PL
通讯作者：
WHITLOW, PL
影响因子：
158.5
作者：
KAMINSKI, MS;ZASADNY, KR;WAHL, RL
通讯作者：
WAHL, RL
影响因子：
4.6
作者：
Coselli, JS;Conklin, LD;LeMaire, SA
通讯作者：
LeMaire, SA
影响因子：
6
作者：
Lee, JS;Basalyga, DM;Vyavahare, NR
通讯作者：
Vyavahare, NR
DOI：
10.1016/s1385-299x(99)00007-0
发表时间：
1999-07-01
期刊：
BRAIN RESEARCH PROTOCOLS
影响因子：
--
作者：
Rosa-Molinar, E;Proskocil, BJ;Fritzsch, B
通讯作者：
Fritzsch, B