Levit Shani L, Yang Hu, Tang Christina
Chemical and Life Science Engineering Department, Virginia Commonwealth University, Richmond, VA 23284, USA.
Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Nanomaterials (Basel). 2020 Mar 20;10(3):561. doi: 10.3390/nano10030561.
Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP < 6) PTX and LAP into polymer nanoparticles with a coordination complex of tannic acid and iron formed during the mixing process. We determine the formulation parameters required to achieve uniform nanoparticles and evaluate the drug release in vitro. The size of the resulting nanoparticles was stable at pH 7.4, facilitating sustained drug release via first-order Fickian diffusion. Encapsulating either PTX or LAP into nanoparticles increases drug potency (as indicated by the decrease in IC-50 concentration); we observe a 1500-fold increase in PTX potency and a six-fold increase in LAP potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than treating with two single-drug-loaded nanoparticles as the combination index is 0.23 compared to 0.40, respectively.
紫杉醇（PTX）制剂泰素是使用最广泛的抗癌药物之一，尤其用于治疗手术后复发性卵巢癌。临床上，PTX与其他药物如拉帕替尼（LAP）联合使用以提高治疗效果。用纳米颗粒递送药物组合有改善化疗结果的潜力。在本研究中，我们使用快速、可扩展的闪式纳米沉淀法，在混合过程中利用单宁酸和铁形成的配位络合物，将弱疏水性药物（logP < 6）PTX和LAP封装到聚合物纳米颗粒中。我们确定了获得均匀纳米颗粒所需的制剂参数，并评估了体外药物释放情况。所得纳米颗粒的尺寸在pH 7.4时稳定，通过一级菲克扩散促进药物持续释放。将PTX或LAP封装到纳米颗粒中可提高药物效力（以IC-50浓度降低表示）；我们观察到PTX效力增加了1500倍，LAP效力增加了6倍。当PTX和LAP共同负载在同一纳米颗粒中时，它们具有协同作用，与分别用两种单药负载纳米颗粒治疗相比，联合指数为0.23，而单药负载纳米颗粒的联合指数分别为0.40，协同作用更强。
