Development of new lipid-based paclitaxel nanoparticles using sequential simplex optimization.
Development of new lipid-based paclitaxel nanoparticles using sequential simplex optimization.
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DOI：
10.1016/j.ejpb.2008.11.012
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Mumper RJ
中科院分区：
文献类型：
--
作者：
Dong X;Mattingly CA;Tseng M;Cho M;Adams VR;Mumper RJ
这些研究的目的是开发由温微乳液前体制备的不含Cremophor的基于脂质的紫杉醇（PX）纳米颗粒制剂。为了识别和优化新的纳米颗粒，结合田口阵列和顺序单纯形优化进行实验设计。结合田口阵列和顺序单纯形优化有效地指导紫杉醇纳米粒的设计。获得了两种优化的紫杉醇纳米粒（NP）：由三十二烷酸甘油酯（GT）和聚氧乙烯20-硬脂基醚（Brij 78）组成的G78 NP和由Miglyol 812、Brij 78和D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）组成的BTM NP。两种纳米粒均成功包封紫杉醇，最终浓度为150 μg/ml（载药量超过6%），粒径小于200 nm，包封率超过85%。如通过物理稳定性所测量的，这些新型紫杉醇纳米颗粒在4°C下稳定超过三个月，并且在37°C下在PBS中稳定超过102小时。紫杉醇的释放是缓慢和持续的，没有初始突释。在MDA-MB-231癌细胞中的细胞毒性研究表明，与Taxol®相比，两种纳米颗粒具有相似的抗癌活性。有趣的是，PX BTM纳米胶囊可以在没有冷冻保护剂的情况下冻干。仅由PX BTM NP在水中组成的冻干粉末可以快速再水化，并完全保留原始理化性质、体外释放性质和细胞毒性特征。序贯单纯形优化已被用于鉴定具有有用属性的有前途的新的基于脂质的紫杉醇纳米颗粒。
The objective of these studies was to develop Cremophor-free lipid-based paclitaxel (PX) nanoparticle formulations prepared from warm microemulsion precursors. To identify and optimize new nanoparticles, experimental design was performed combining Taguchi array and sequential simplex optimization. The combination of Taguchi array and sequential simplex optimization efficiently directed the design of paclitaxel nanoparticles. Two optimized paclitaxel nanoparticles (NPs) were obtained: G78 NPs composed of glyceryl tridodecanoate (GT) and polyoxyethylene 20-stearyl ether (Brij 78), and BTM NPs composed of Miglyol 812, Brij 78 and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Both nanoparticles successfully entrapped paclitaxel at a final concentration of 150 μg/ml (over 6% drug loading) with particle sizes less than 200 nm and over 85% of entrapment efficiency. These novel paclitaxel nanoparticles were stable at 4°C over three months and in PBS at 37°C over 102 hours as measured by physical stability. Release of paclitaxel was slow and sustained without initial burst release. Cytotoxicity studies in MDA-MB-231 cancer cells showed that both nanoparticles have similar anticancer activities compared to Taxol®. Interestingly, PX BTM nanocapsules could be lyophilized without cryoprotectants. The lyophilized powder comprised only of PX BTM NPs in water could be rapidly rehydrated with complete retention of original physicochemical properties, in-vitro release properties, and cytotoxicity profile. Sequential Simplex Optimization has been utilized to identify promising new lipid-based paclitaxel nanoparticles having useful attributes.
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