PDF(Pubmed)
Abstract：
Erythrocytes are impressive tools for drug delivery, especially to macrophages. Therefore, berberine was loaded into erythrocytes using both hypotonic pre-swelling and endocytosis methods to target macrophages. Physicochemical and kinetic parameters of the resulting carrier cells, such as drug loading/release kinetics, osmotic fragility, and hematological indices, were determined. Drug loading was optimized for the study using Taguchi experimental design and lab experiments. Loaded erythrocytes were targeted to macrophages using ZnCl2 and bis-sulfosuccinimidyl-suberate, and targeting was evaluated using flow cytometry and Wright-Giemsa staining. Differentiated macrophages were stimulated with lipopolysaccharide, and the inflammatory profiles of macrophages were evaluated using ELISA, western blotting, and real-time PCR. Findings indicated that the endocytosis method is preferred due to its low impact on the erythrocyte\'s structural integrity. Maximum loading achieved (1386.68 ± 22.43 μg/ml) at 1500 μg/ml berberine treatment at 37 °C for 2 h. Berberine successfully inhibited NF-κB translation in macrophages, and inflammatory response markers such as IL-1β, IL-8, IL-23, and TNF-α were decreased by approximately ninefold, sixfold, twofold, eightfold, and twofold, respectively, compared to the LPS-treated macrophages. It was concluded that berberine-loaded erythrocytes can effectively target macrophages and modulate the inflammatory response.
摘要：
红细胞是令人印象深刻的药物输送工具，尤其是巨噬细胞。因此,使用低渗前肿胀和内吞方法将小檗碱加载到红细胞中以靶向巨噬细胞。所得载体细胞的物理化学和动力学参数，如药物加载/释放动力学，渗透脆弱性，和血液学指标，决心。使用Taguchi实验设计和实验室实验对研究的药物负载进行了优化。使用ZnCl2和双-磺基琥珀酰亚胺酯将负载的红细胞靶向巨噬细胞，使用流式细胞术和Wright-Giemsa染色评估靶向性。分化的巨噬细胞用脂多糖刺激，使用ELISA评估巨噬细胞的炎症特征，西方印迹,和实时PCR。研究结果表明，内吞方法是优选的，因为它对红细胞结构完整性的影响很小。1500μg/ml小檗碱在37°C处理2h时达到最大负荷（1386.68±22.43μg/ml）。小檗碱成功抑制巨噬细胞中NF-κB的翻译，和炎症反应标志物如IL-1β，IL-8，IL-23和TNF-α降低了大约九倍，六倍，双重,八倍，和双重，分别,与LPS处理的巨噬细胞相比。结论小檗碱负载红细胞能有效靶向巨噬细胞，调节炎症反应。
