PEG-PLA diblock copolymer micelle-like nanoparticles as all-trans-retinoic acid carrier: in vitro and in vivo characterizations
PEG-PLA diblock copolymer micelle-like nanoparticles as all-trans-retinoic acid carrier: in vitro and in vivo characterizations
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作为全反式视黄酸载体的 PEG-PLA 二嵌段共聚物胶束状纳米粒子：体外和体内表征
DOI：
10.1088/0957-4484/20/5/055106
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发表时间：
2009-02-04
期刊：
影响因子：
3.5
通讯作者：
Nagai, Tsuneji
中科院分区：
文献类型：
--
作者：
Li, Yuan;Qi, Xian Rong;Nagai, Tsuneji
本研究的目的是表征的性质在体外，即释放，降解，溶血潜力和抗癌活性，并在大鼠体内处置全反式维甲酸（ATRA）后，全反式维甲酸胶束样纳米粒给药。两亲性嵌段共聚物由形成胶束壳的mPEG嵌段和形成核的PLA嵌段组成。通过丙酮挥发透析法制备的mPEG-PLA纳米粒经1H NMR谱鉴定为具有核壳结构。考察了临界缔合浓度、载药量、载药量、粒径和包封率等性能。纳米粒中ATRA的释放和PLA的降解主要与纳米粒的组成有关。共聚物分子量越小，药物含量越低，ATRA释放越快。在体外，ATRA在mPEG-PLA纳米粒中的掺入降低了ATRA的溶血潜力。包封后ATRA对HepG 2细胞的抗肿瘤活性增强，表明ATRA的抗肿瘤作用增强。在体内，静脉注射给大鼠后，ATRA-负载mPEG-PLA纳米粒的血流中ATRA的水平和生物利用度高于ATRA溶液。总之，mPEG-PLA二嵌段共聚物的结构可以被调节以适应纳米颗粒的体外和体内表征的需求。mPEG-PLA纳米粒载ATRA具有良好的注射给药前景。
The purpose of this study was to characterize the properties in vitro, i.e. release, degradation, hemolytic potential and anticancer activity, and in vivo disposition of all-trans-retinoic acid (ATRA) in rats after administration of ATRA-loaded micelle-like nanoparticles. The amphiphilic block copolymers consisted of a micellar shell-forming mPEG block and a core-forming PLA block. The mPEG–PLA nanoparticles prepared by an acetone volatilization dialysis procedure were identified as having core–shell structure by 1H NMR spectroscopy. Critical association concentration, drug contents, loading efficiency, particle size and ξ potential were evaluated. The release of ATRA from the nanoparticles and the degradation of PLA were found to be mostly associated with the compositions of the nanoparticles. ATRA release was faster at smaller molecular weight of copolymer and lower drug contents. In vitro, the incorporation of ATRA in mPEG–PLA nanoparticles reduced the hemolytic potential of ATRA. Furthermore, anticancer activity of ATRA against HepG2 cell was increased by encapsulation, which showed an enhancement of tumor treatment of ATRA. In vivo, after intravenous injection to rats, the levels of ATRA in the blood stream and the bioavailability were higher for ATRA-loaded mPEG–PLA nanoparticles than those for ATRA solution. In conclusion, the structure of the mPEG–PLA diblock copolymer could be modulated to fit the demand of in vitro and in vivo characterizations of nanoparticles. The mPEG–PLA nanoparticles’ loading ATRA have a promising future for injection administration.