PLGA/liposome hybrid nanoparticles for short-chain ceramide delivery.

PLGA/liposome hybrid nanoparticles for short-chain ceramide delivery.
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DOI:
10.1007/s11095-013-1190-5
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发表时间:
2014-03
影响因子:
3.7
通讯作者:
Sun, Duxin
Sun, Duxin
中科院分区:
医学3区
文献类型:
--
作者:
Zou, Peng;Stern, Stephan T.;Sun, Duxin

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亲脂性药物从脂质体脂质双层快速过早释放到血浆蛋白和生物膜是靶向药物递送的挑战。本研究的目的是通过聚乳酸-乙醇酸 (PLGA) 将神经酰胺封装到脂质体水性内部,从而减少亲脂性短链神经酰胺的过早释放。将 BODIPY FL 标记的神经酰胺(FL-神经酰胺)和 BODIPY-TR 标记的神经酰胺(TR-神经酰胺)封装在羧基末端的 PLGA 纳米颗粒中。然后将带负电荷的 PLGA 纳米颗粒封装到阳离子脂质体中以获得 PLGA/脂质体杂化物。作为对照,制备了不含 PLGA 的 FL-神经酰胺和/或 TR 神经酰胺共负载脂质体。使用 FL-神经酰胺(供体)和 TR-神经酰胺(受体)之间的荧光共振能量转移 (FRET) 比较大鼠血浆、培养的 MDA-MB-231 细胞和大鼠血液循环中 PLGA/脂质体杂合体和脂质体的神经酰胺释放。 FRET分析表明,脂质体脂质双层中的FL-神经酰胺和TR-神经酰胺在与大鼠血浆孵育期间迅速释放。相比之下,PLGA/脂质体混合物中的FL-神经酰胺和TR-神经酰胺显示出延长释放。细胞的 FRET 图像显示,脂质体双层中的神经酰胺迅速转移到细胞膜上。相比之下,PLGA/脂质体混合物中的神经酰胺与纳米粒子同时内化到细胞中。给大鼠静脉注射后,包裹在脂质体双层中的神经酰胺在 2 分钟内完全释放。相比之下,封装在 PLGA 核心中的神经酰胺在 PLGA/脂质体混合物中保留 4 小时。 PLGA/脂质体混合纳米颗粒减少了神经酰胺在体外和体内的过早释放,并为亲脂性药物的靶向递送提供了可行的平台。
Rapid premature release of lipophilic drugs from liposomal lipid bilayer to plasma proteins and biological membranes is a challenge for targeted drug delivery. The purpose of this study is to reduce premature release of lipophilic short-chain ceramides by encapsulating ceramides into liposomal aqueous interior with the aid of poly( lactic-coglycolicacid) (PLGA). BODIPY FL labeled ceramide (FL-ceramide) and BODIPY-TR labeled ceramide (TR-ceramide) were encapsulated into carboxy-terminated PLGA nanoparticles. The negatively charged PLGA nanoparticles were then encapsulated into cationic liposomes to obtain PLGA/liposome hybrids. As a control, FL-ceramide and/or TR ceramide co-loaded liposomes without PLGA were prepared. The release of ceramides from PLGA/liposome hybrids and liposomes in rat plasma, cultured MDA-MB-231 cells, and rat blood circulation was compared using fluorescence resonance energy transfer (FRET) between FL-ceramide (donor) and TR-ceramide (acceptor). FRET analysis showed that FL-ceramide and TR-ceramide in liposomal lipid bilayer were rapidly released during incubation with rat plasma. In contrast, the FL-ceramide and TR-ceramide in PLGA/liposome hybrids showed extended release. FRET images of cells revealed that ceramides in liposomal bilayer were rapidly transferred to cell membranes. In contrast, ceramides in PLGA/liposome hybrids were internalized into cells with nanoparticles simultaneously. Upon intravenous administration to rats, ceramides encapsulated in liposomal bilayer were completely released in 2 minutes. In contrast, ceramides encapsulated in the PLGA core were retained in PLGA/liposome hybrids for 4 hours. The PLGA/liposome hybrid nanoparticles reduced in vitro and in vivo premature release of ceramides and offer a viable platform for targeted delivery of lipophilic drugs.
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发表时间: 2011-03-16
影响因子: 4.7
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发表时间: 2010-11-01
期刊: BIOMATERIALS
影响因子: 14
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