Di Mauro Primiano Pio, Borrós Salvador
Sagetis-Biotech; Grup d'Enginyeria de Materials (GEMAT) Institut Quimic de Sarria, Universidad Ramon Llull, Via Augusta 390, 08017, Barcelona, Spain,
Pharm Res. 2014 Dec;31(12):3461-77. doi: 10.1007/s11095-014-1434-z. Epub 2014 Jun 18.
The objective of this study was to develop a custom-tailored polymeric drug delivery system for paclitaxel, employing a novel biodegradable block co-polymer (P), intended to be intravenously administered, capable of improving therapeutic index of the drug and devoid of the adverse effect of an uncontrolled release.
Paclitaxel loaded nanoparticles (PTX-NPs) were prepared by a modified nanoprecipitation method and emulsification-solvent evaporation method. Our approach involves a focusing on the formulation parameters that can be modified in order to obtain completely customized NPs in terms of size, zeta-potential, drug content and release profile. The biocompatibility and anti-proliferative efficiency of PTX-NPs against glioblastoma cell line were evaluated in vitro by MTS.
All formulations showed spherical nanometric (<200 nm), monodisperse (~0.1), Poly (Ethylene Glycol) (PEG)-coated and negatively charged particles. Selected NPs revealed higher PTX content (up to 24%) in comparison with polyester-based NPs. The release behaviour of PTX from the developed NPs exhibited an approximately first-order profile, without initial burst and characterized by a slow and constant release. Hydrophobic character of the NPs can be set in order to achieve a slower and more controlled release for a prolonged period of time. PTX-NPs were hemocompatible and had significant in vitro anti-tumoral activity against human primary glioblastoma cell line (U-87 MG); cytotoxicity was in time- and drug concentration- dependent manner.
The developed drug delivery system proved to be suitable for intravenous administration. NPs characteristics can be customized to obtain high PTX loaded NPs that can improve therapeutic index and avoid an uncontrolled release.
本研究的目的是开发一种针对紫杉醇的定制化聚合物药物递送系统，采用一种新型可生物降解的嵌段共聚物（P），旨在静脉给药，能够提高药物的治疗指数且无控释的不良反应。
采用改良的纳米沉淀法和乳化溶剂蒸发法制备载紫杉醇纳米粒（PTX-NPs）。我们的方法着重于可修改的制剂参数，以便在尺寸、zeta电位、药物含量和释放曲线方面获得完全定制的纳米粒。通过MTS体外评估PTX-NPs对胶质母细胞瘤细胞系的生物相容性和抗增殖效率。
所有制剂均显示为球形纳米级（<200 nm）、单分散（~0.1）、聚乙二醇（PEG）包被且带负电荷的颗粒。与聚酯基纳米粒相比，所选纳米粒显示出更高的PTX含量（高达24%）。PTX从所开发纳米粒中的释放行为呈现近似一级曲线，无初始突释，其特征为缓慢且持续释放。可设定纳米粒的疏水性以实现更长时间的更缓慢且更可控的释放。PTX-NPs具有血液相容性，对人原发性胶质母细胞瘤细胞系（U-87 MG）具有显著的体外抗肿瘤活性；细胞毒性呈时间和药物浓度依赖性。
所开发的药物递送系统被证明适用于静脉给药。可定制纳米粒的特性以获得高载药量的PTX纳米粒，从而提高治疗指数并避免无控释。
