Bhavsar Mayank D, Tiwari Sandip B, Amiji Mansoor M
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, United States.
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, United States.
J Control Release. 2006 Jan 10;110(2):422-430. doi: 10.1016/j.jconrel.2005.11.001. Epub 2005 Dec 9.
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 mum in size, which could be used as oral delivery system for therapeutic and antigenic macromolecules.
在生物技术领域，随着治疗性和抗原性蛋白质的发现取得了巨大进展，这推动了为这些及其他大分子开发合适口服给药装置的需求。在本研究中，我们报告了通过类似双乳液技术将异硫氰酸荧光素（FITC）标记的明胶纳米颗粒包封到聚（ε-己内酯）（PCL）微球中（纳米颗粒-微球口服给药系统，NiMOS），并使用3(3)随机全因子设计研究了诸如有机相中聚合物浓度、作为内相添加的纳米颗粒量以及匀化速度等变量对NiMOS粒径的影响。推导了一个包含交互项的统计模型来预测混合系统的粒径。多元线性回归分析和学生t检验的结果表明，为了获得较大粒径的NiMOS，需要高聚合物浓度和低匀化速度。相反，为了获得较小粒径的颗粒，发现高匀化速度非常重要。所获得的数学模型经验证可用于粒径预测。通过荧光显微镜确认了明胶纳米颗粒在PCL微球中的包封情况。基于统计模型，我们还成功制备了尺寸小于10μm的NiMOS，其可作为治疗性和抗原性大分子的口服给药系统。
