Andrew Jennifer S, Anglin Emily J, Wu Elizabeth C, Chen Michelle Y, Cheng Lingyun, Freeman William R, Sailor Michael J
Department of Chemistry and Biochemistry, University of California, San Diego, 9500, Gilman Dr, La Jolla, CA 92093 (USA).
Adv Funct Mater. 2010 Sep 8;20(23):4168-4174. doi: 10.1002/adfm.201000907.
Nanostructured mesoporous silica (SiO(2)) films are used to load and release the monoclonal antibody bevacizumab (Avastin) in vitro. A biocompatible and biodegradable form of mesoporous SiO(2) is prepared by electrochemical etching of single crystalline Si, followed by thermal oxidation in air at 800 °C. Porous SiO(2) exhibits a negative surface charge at physiological pH (7.4), allowing it to spontaneously adsorb the positively charged antibody from an aqueous phosphate buffered saline solution. This electrostatic adsorption allows bevacizumab to be concentrated by >100× (300 mg bevacziumab per gram of porous SiO(2) when loaded from a 1 mg mL(-1) solution of bevacziumab). Drug loading is monitored by optical interferometric measurements of the thin porous film. A two-component Bruggeman effective medium model is employed to calculate percent porosity and film thickness, and is further used to determine the extent of drug loading into the porous SiO(2) film. In vitro drug release profiles are characterized by an enzyme-linked immunosorbent assay (ELISA), which confirms that the antibody is released in its active, VEGF-binding form. The nanostructured delivery system described here provides a sustained release of the monoclonal antibody where approximately 98% of drug is released over a period of one month.
纳米结构的介孔二氧化硅(SiO₂)薄膜用于在体外加载和释放单克隆抗体贝伐单抗(阿瓦斯汀)。通过对单晶硅进行电化学蚀刻,然后在800℃的空气中进行热氧化,制备出具有生物相容性和可生物降解性的介孔SiO₂。在生理pH值(7.4)下,多孔SiO₂呈现负表面电荷,使其能够从磷酸缓冲盐水溶液中自发吸附带正电荷的抗体。这种静电吸附使贝伐单抗的浓度提高了100倍以上(当从1mg/mL的贝伐单抗溶液加载时,每克多孔SiO₂可吸附300mg贝伐单抗)。通过对多孔薄膜进行光学干涉测量来监测药物负载情况。采用双组分布鲁格曼有效介质模型计算孔隙率百分比和薄膜厚度,并进一步用于确定药物加载到多孔SiO₂薄膜中的程度。体外药物释放曲线通过酶联免疫吸附测定(ELISA)进行表征,该测定证实抗体以其具有VEGF结合活性的形式释放。本文所述的纳米结构递送系统可实现单克隆抗体的持续释放,在一个月的时间内约98%的药物被释放。