Hamoudeh Misara, Diab Roudayna, Fessi Hatem, Dumontet Charles, Cuchet Delphine
Pharmaceutics and Pharmaceutical Technology Department, LAGEP, Laboratoire d'Automatique et de Genie de Procedes, UMR CNRS, Universite Claude Bernard Lyon1, CPE-Lyon, Villeurbanne, France.
Drug Dev Ind Pharm. 2008 Jul;34(7):698-707. doi: 10.1080/03639040701842444.
In our pursuit to develop suitable therapeutic particulate systems for intratumoral delivery by the targeted multi-therapy (TMT) technique, we describe the preparation of paclitaxel-loaded poly(D,L-lactic-co-glycolic) acid (PLGA) microparticles (MPs) (drug loading 35-38%, wt/wt; size 0.7-5 microm). Magnetite (15%, wt/wt) was also incorporated in some preparations for a future magnetic resonance imaging (MRI)-guided delivery. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) experiments showed that paclitaxel was not encapsulated in its initial crystalline form. The paclitaxel in vitro release pattern showed a biphasic tendency with a burst effect followed by a sustained release (28% released amount after 1 month), which was accompanied with MP erosion and degradation signs as confirmed by scanning electronic microscopy (SEM) micrographs. The paclitaxel-loaded MPs demonstrated a dose-dependent antitumor effect on human uterine cancer cells, with an IC(50) value relatively close to that of commercial Taxol. This paclitaxel delivery system represents a potent antiprofilerative and radiosensitizer agent for intratumoral administration via the TMT technique.
在我们致力于通过靶向多疗法（TMT）技术开发适用于肿瘤内递送的治疗性微粒系统的过程中，我们描述了载有紫杉醇的聚（D，L-乳酸-共-乙醇酸）（PLGA）微粒（MPs）的制备方法（药物负载量为35-38%，重量/重量；尺寸为0.7-5微米）。在一些制剂中还加入了磁铁矿（15%，重量/重量），用于未来的磁共振成像（MRI）引导递送。X射线衍射（XRD）和差示扫描量热法（DSC）实验表明，紫杉醇不是以其初始结晶形式被包裹的。紫杉醇的体外释放模式呈现出双相趋势，先是有一个突释效应，随后是持续释放（1个月后释放量为28%），扫描电子显微镜（SEM）显微照片证实这伴随着MP的侵蚀和降解迹象。载有紫杉醇的MPs对人子宫癌细胞表现出剂量依赖性的抗肿瘤作用，其半数抑制浓度（IC50）值相对接近市售紫杉醇。这种紫杉醇递送系统是一种通过TMT技术进行肿瘤内给药的强效抗增殖和放射增敏剂。
