School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
J Am Chem Soc. 2013 May 29;135(21):7933-7. doi: 10.1021/ja401422r. Epub 2013 May 15.
Simultaneous encapsulation of multiple active substances in a single carrier is essential for therapeutic applications of synergistic combinations of drugs. However, traditional carrier systems often lack efficient encapsulation and release of incorporated substances, particularly when combinations of drugs must be released in concentrations of a prescribed ratio. We present a novel biodegradable core-shell carrier system fabricated in a one-step, solvent-free process on a microfluidic chip; a hydrophilic active (doxorubicin hydrochloride) is encapsulated in the aqueous core, while a hydrophobic active (paclitaxel) is encapsulated in the solid shell. Particle size and composition can be precisely controlled, and core and shell can be individually loaded with very high efficiency. Drug-loaded particles can be dried and stored as a powder. We demonstrate the efficacy of this system through the simultaneous encapsulation and controlled release of two synergistic anticancer drugs using two cancer-derived cell lines. This solvent-free platform technology is also of high potential value for encapsulation of other active ingredients and chemical reagents.
同时将多种活性物质封装在单个载体中对于协同药物组合的治疗应用至关重要。然而,传统的载体系统通常缺乏对所包含物质的有效封装和释放,特别是当必须以规定比例的浓度释放药物组合时。我们提出了一种新颖的可生物降解的核壳载体系统,该系统在微流控芯片上通过一步无溶剂工艺制造;亲水性活性物质(盐酸多柔比星)被封装在水核中,而疏水性活性物质(紫杉醇)被封装在固体壳中。可以精确控制颗粒大小和组成,并且可以非常高效地单独装载核和壳。载药颗粒可以干燥并储存为粉末。我们通过使用两种源自癌细胞系的方法来展示该系统同时封装和控制两种协同抗癌药物的功效。这种无溶剂平台技术对于封装其他活性成分和化学试剂也具有很高的潜在价值。