Lee Chia-Ying, Tsai Tsuimin, Peng Po-Chun, Chen Chin-Tin
Department of Biochemical Science and Technology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
FormuRx Pharmaceuticals Co., Ltd., Taipei 10617, Taiwan.
Biomedicines. 2022 May 27;10(6):1259. doi: 10.3390/biomedicines10061259.
Doxorubicin (Dox) is a widely known chemotherapeutic drug that has been encapsulated into liposomes for clinical use, such as Doxil and Myocet. Both of these are prepared via remote loading methods, which require multistep procedures. Additionally, their antitumor efficacy is hindered due to the poor drug release from PEGylated liposomes in the tumor microenvironment. In this study, we aimed to develop doxorubicin-loaded lipid-based nanocarriers (LNC-Dox) based on electrostatic interaction using microfluidic technology. The resulting LNC-Dox showed high loading capacity, with a drug-to-lipid ratio (D/L ratio) greater than 0.2, and high efficacy of drug release in an acidic environment. Different lipid compositions were selected based on critical packing parameters and further studied to outline their effects on the physicochemical characteristics of LNC-Dox. Design of experiments was implemented for formulation optimization. The optimized LNC-Dox showed preferred release in acidic environments and better therapeutic efficacy compared to PEGylated liposomal Dox in vivo. Thus, this study provides a feasible approach to efficiently encapsulate doxorubicin into lipid-based nanocarriers fabricated by microfluidic rapid mixing.
阿霉素（Dox）是一种广为人知的化疗药物，已被封装到脂质体中用于临床，如多柔比星脂质体（Doxil）和表柔比星脂质体（Myocet）。这两种制剂都是通过远程加载方法制备的，需要多步程序。此外，由于聚乙二醇化脂质体在肿瘤微环境中药物释放不佳，它们的抗肿瘤疗效受到阻碍。在本研究中，我们旨在利用微流控技术基于静电相互作用开发载阿霉素的脂质基纳米载体（LNC-Dox）。所得的LNC-Dox显示出高载药量，药物与脂质比（D/L比）大于0.2，并且在酸性环境中具有高效的药物释放。基于临界堆积参数选择了不同的脂质组成，并进一步研究以概述它们对LNC-Dox物理化学特性的影响。实施实验设计以优化制剂。与聚乙二醇化脂质体阿霉素相比，优化后的LNC-Dox在体内显示出在酸性环境中的优先释放和更好的治疗效果。因此，本研究提供了一种可行的方法，可将阿霉素有效地封装到通过微流控快速混合制备的脂质基纳米载体中。
