Wang Hao, Yao Qing, Zhu Wenquan, Yang Yang, Gao Chunsheng, Han Cuiyan, Chu Xiaoyang
College of Pharmacy, Qiqihar Medical University, 161006, Qiqihar, China.
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
AAPS PharmSciTech. 2022 Nov 30;24(1):12. doi: 10.1208/s12249-022-02466-8.
Chronic lead poisoning has become a major factor in global public health. Chelation therapy is usually used to manage lead poisoning. Dimercaptosuccinic acid (DMSA) is a widely used heavy metal chelation agent. However, DMSA has the characteristics of poor water solubility, low oral bioavailability, and short half-life, which limit its clinical application. Herein, a long-cycle slow-release nanodrug delivery system was constructed. We successfully coated the red blood cell membrane (RBCM) onto the surface of dimercaptosuccinic acid polylactic acid glycolic acid copolymer (PLGA) nanoparticles (RBCM-DMSA-NPs), which have a long cycle and detoxification capabilities. The NPs were characterized and observed by particle size meters and transmission electron microscopy. The results showed that the particle size of RBCM-DMSA-NPs was approximately 146.66 ± 2.41 nm, and the zeta potential was - 15.34 ± 1.60 mV. The homogeneous spherical shape and clear core-shell structure of the bionic nanoparticles were observed by transmission electron microscopy. In the animal tests, the area under the administration time curve of RBCM-DMSA-NPs was 156.52 ± 2.63 (mg/L·h), which was 5.21-fold and 2.36-fold that of free DMSA and DMSA-NPs, respectively. Furthermore, the median survival of the RBCM-DMSA-NP treatment group (47 days) was 3.61-fold, 1.32-fold, and 1.16-fold for the lead poisoning group, free DMSA, and DMSA-NP groups, respectively. The RBCM-DMSA-NP treatment significantly extended the cycle time of the drug in the body and improved the survival rate of mice with chronic lead poisoning. Histological analyses showed that RBCM-DMSA-NPs did not cause significant systemic toxicity. These results indicated that RBCM-DMSA-NPs could be a potential candidate for long-term chronic lead exposure treatment.
慢性铅中毒已成为全球公共卫生的一个主要因素。螯合疗法通常用于治疗铅中毒。二巯基丁二酸（DMSA）是一种广泛使用的重金属螯合剂。然而，DMSA具有水溶性差、口服生物利用度低和半衰期短的特点，这限制了其临床应用。在此，构建了一种长周期缓释纳米药物递送系统。我们成功地将红细胞膜（RBCM）包覆在二巯基丁二酸聚乳酸乙醇酸共聚物（PLGA）纳米颗粒（RBCM-DMSA-NPs）表面，该纳米颗粒具有长循环和解毒能力。通过粒度仪和透射电子显微镜对纳米颗粒进行了表征和观察。结果表明，RBCM-DMSA-NPs的粒径约为146.66±2.41nm，zeta电位为-15.34±1.60mV。通过透射电子显微镜观察到仿生纳米颗粒具有均匀的球形和清晰的核壳结构。在动物试验中，RBCM-DMSA-NPs给药时间曲线下面积为156.52±2.63（mg/L·h），分别是游离DMSA和DMSA-NPs的5.21倍和2.36倍。此外，RBCM-DMSA-NP治疗组的中位生存期（47天）分别是铅中毒组、游离DMSA组和DMSA-NP组的3.61倍、1.32倍和1.16倍。RBCM-DMSA-NP治疗显著延长了药物在体内的循环时间，提高了慢性铅中毒小鼠的存活率。组织学分析表明，RBCM-DMSA-NPs不会引起明显的全身毒性。这些结果表明，RBCM-DMSA-NPs可能是长期慢性铅暴露治疗的潜在候选药物。
