Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design
Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design
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DOI：
10.1016/j.jconrel.2005.11.001
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发表时间：
2006-01-10
影响因子：
10.8
通讯作者：
Amiji, MM
中科院分区：
文献类型：
--
作者：
Bhavsar, MD;Tiwari, SB;Amiji, MM
在生物技术领域中关于发现治疗性和抗原性蛋白质的巨大进展已经推动了开发用于这些和其它大分子的合适的口服递送装置的需要。在这项研究中，我们报告了荧光素异硫氰酸酯（FITC）标记的明胶纳米粒子封装到聚己内酯微球（纳米颗粒-微球口服递送系统，NiMOS）的影响，以及变量如有机相中的聚合物浓度，作为内相添加的纳米颗粒的量，和均匀化速度对NiMOS颗粒尺寸的影响。建立了含相互作用项的混合体系颗粒尺寸的统计模型。多元线性回归分析和学生t检验的结果表明，为了获得大颗粒的NiMOS，高的聚合物浓度和低的均化速度是必要的。相反，为了获得更小尺寸的颗粒，发现高速均化是非常重要的。对所建立的数学模型进行了验证，并用于颗粒尺寸的预测。通过荧光显微镜证实了明胶纳米颗粒在PCL微球中的包封。基于统计模型，我们还成功地生产尺寸小于10 μ m的NiMOS，其可用作治疗性和抗原性大分子的口服递送系统。(c)2005 Elsevier B. V.保留所有权利。
The tremendous progress witnessed in the field of biotechnology with respect to discovery of therapeutic and antigenic proteins has propelled the need for development of suitable oral delivery devices for these and other macromolecules. In this study, we report the encapsulation of fluorescein isothiocyanate (FITC)-labeled gelatin nanoparticles into poly(epsilon-caprolactone) (PCL) microsphere (nanoparticle-in-microsphere oral delivery system, NiMOS) by double emulsion like technique and the influence of variables such as polymer concentration in organic phase, amount of nanoparticles added as internal phase, and the speed of homogenization on particle size of NiMOS using a 3(3) randomized full factorial design. A statistical model with interaction terms was derived to predict the particle size of the hybrid system. The results from multiple linear regression analysis and Student's t-test revealed that for obtaining large particles of NiMOS, a high polymer concentration and low speed of homogenization was necessary. In contrast, to obtain particles of smaller size, high speed of homogenization was found to be very important. The mathematical model obtained was validated for prediction of particle size. The encapsulation of gelatin nanoparticles in PCL microsphere was confirmed by fluorescent microscopy. Based on the statistical model we were also successful in producing NiMOS of less than 10 mu m in size, which could be used as oral delivery system for therapeutic and antigenic macromolecules. (c) 2005 Elsevier B.V. All rights reserved.