Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, People's Republic of China.
Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China.
Int J Nanomedicine. 2022 Nov 14;17:5265-5286. doi: 10.2147/IJN.S369761. eCollection 2022.
Paclitaxel (PTX) has been widely utilized for the treatment of breast cancer. However, drawbacks, such as poor aqueous solubility, rapid blood clearance and severe toxicity, greatly reduce its efficacy and safety. Herein, a novel self-developed curcumin derivative (CUD) was chosen as the carrier to develop a long-acting PTX nano-delivery system (PTX-Sln@CUD) in order to improve its pharmacokinetic behavior, anti-breast cancer efficacy and safety.
PTX-Sln@CUD was prepared using solid dispersion and ultrasonic technology. Relevant physical and chemical properties, including stability and release behavior, were characterized. The clearance of PTX-Sln@CUD in vivo was studied by pharmacokinetic experiments. The anti-tumor activity of PTX-Sln@CUD was investigated in vitro and in vivo. Hemolysis experiments, acute toxicity and cumulative toxicity studies were performed in mice to determine the safety of PTX-Sln@CUD.
The average particle size, PDI, Zeta potential, encapsulation efficiency and loading efficiency of the PTX-Sln@CUD were 238.5 ± 4.79 nm, 0.225 ± 0.011, -33.8 ± 1.26 mV, 94.20 ± 0.49% and 10.98 ± 0.31%, respectively. PTX-Sln@CUD was found to be stable at room temperature for half a year. The cumulative release rates of PTX-Sln@CUD at 24, 96 and 168 h were 17.98 ± 2.60, 57.09 ± 2.32 and 72.66 ± 4.16%, respectively, which were adherent to zero-order kinetics. T, MRT and AUC of the PTX-Sln@CUD group were 4.03-fold (44.293 h), 7.78-fold (38.444 h) and 6.18-fold (14.716 mg/L*h) of the PTX group, respectively. PTX-Sln@CUD group demonstrated stronger anti-breast cancer activity than the PTX group. Importantly, the PTX-Sln@CUD group was safer compared to the PTX group both in vitro and in vivo.
PTX-Sln@CUD was verified as promising therapeutic nanoparticles for breast cancer and provided a novel strategy to solve the problem of low efficacy and poor safety of clinical chemotherapy drugs.
紫杉醇（PTX）已广泛用于乳腺癌的治疗。然而，其较差的水溶性、快速的血液清除率和严重的毒性等缺点，极大地降低了其疗效和安全性。在此，选择一种新型的姜黄素衍生物（CUD）作为载体，开发了一种长效紫杉醇纳米递药系统（PTX-Sln@CUD），以改善其药代动力学行为、抗乳腺癌疗效和安全性。
采用固体分散和超声技术制备 PTX-Sln@CUD。对其相关理化性质，包括稳定性和释放行为进行了表征。通过药代动力学实验研究了 PTX-Sln@CUD 在体内的清除情况。在体外和体内研究了 PTX-Sln@CUD 的抗肿瘤活性。通过溶血实验、急性毒性和累积毒性实验研究，评估了 PTX-Sln@CUD 的安全性。
PTX-Sln@CUD 的平均粒径、PDI、Zeta 电位、包封率和载药量分别为 238.5±4.79nm、0.225±0.011、-33.8±1.26mV、94.20±0.49%和 10.98±0.31%。室温下放置半年，PTX-Sln@CUD 稳定。PTX-Sln@CUD 在 24、96 和 168h 的累积释放率分别为 17.98±2.60%、57.09±2.32%和 72.66±4.16%，符合零级动力学。PTX-Sln@CUD 组的 T 1/2、MRT 和 AUC 分别是 PTX 组的 4.03 倍（44.293h）、7.78 倍（38.444h）和 6.18 倍（14.716mg/L*h）。PTX-Sln@CUD 组的抗乳腺癌活性强于 PTX 组。重要的是，PTX-Sln@CUD 组在体内外均比 PTX 组更安全。
PTX-Sln@CUD 被证实为有前途的乳腺癌治疗纳米粒，为解决临床化疗药物疗效低、安全性差的问题提供了新策略。
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