a School of Pharmacy , Shanghai Jiao Tong University , Shanghai , China.
b Department of Pharmacy , Shaheed Benazir Bhutto University , Sheringal Dir (Upper) , Pakistan.
Drug Deliv. 2019 Dec;26(1):199-207. doi: 10.1080/10717544.2019.1573861.
The multidrug resistance in tumor (MDR) is a major barrier to efficient cancer therapy. Modern pharmacological studies have proven that tetrandrine (TET) has great potential in reversing MDR. However, it has a series of medication problems in clinic such as poor water solubility, low oral bioavailability and short half-life in vivo. Aiming at the above problems, red blood cell membrane-camouflaged TET-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (RPTNs) had been developed. The RPTNs had spherical shell-core double layer structure with average particle size of 164.1 ± 1.65 nm and encapsulation efficiency of 84.1% ± 0.41%. Compared with TET-PLGA nanoparticles (PTNs), the RPTNs reduced RAW 264.7 macrophages' swallowing by 32% due to its retention of natural membrane proteins. The cumulative drug release of RPTNs was 81.88% within 120 h. And pharmacokinetic study showed that the blood half-life of RPTNs was 19.38 h, which was 2.95 times of free drug. When RPTNs of 2 μg/mL TET were administered in combination with adriamycin (ADR), significant MDR reversal effect was observed in drug-resistant cells MCF-7/ADR. In a word, the RPTNs hold potential to improve its efficacy and broaden its clinical application.
肿瘤多药耐药（MDR）是有效癌症治疗的主要障碍。现代药理学研究证明，汉防己甲素（TET）在逆转 MDR 方面具有巨大潜力。然而，它在临床上存在一系列用药问题，如水溶性差、口服生物利用度低和体内半衰期短。针对上述问题，已经开发了红细胞膜伪装的载汉防己甲素聚乳酸-羟基乙酸共聚物（PLGA）纳米粒（RPTNs）。RPTNs 具有球形核壳双层结构，平均粒径为 164.1±1.65nm，包封率为 84.1%±0.41%。与 TET-PLGA 纳米粒（PTNs）相比，由于保留了天然膜蛋白，RPTNs 使 RAW 264.7 巨噬细胞的吞噬作用减少了 32%。RPTNs 在 120h 内的累积药物释放率为 81.88%。药代动力学研究表明，RPTNs 的血半衰期为 19.38h，是游离药物的 2.95 倍。当以 2μg/mL TET 的 RPTNs 与阿霉素（ADR）联合给药时，在耐药细胞 MCF-7/ADR 中观察到明显的 MDR 逆转作用。总之，RPTNs 具有提高疗效和拓宽临床应用的潜力。
