Que Yunduan, Yang Yuhang, Zafar Hajra, Wang Dongming
Department of Orthopedics, Nanjing Gaochun People's Hospital, Gaochun Economic Development Zone, Nanjing, China.
School of Pharmacy, Jiangsu University, Zhenjiang, China.
Front Pharmacol. 2022 Sep 14;13:993095. doi: 10.3389/fphar.2022.993095. eCollection 2022.
We aimed to create a nano drug delivery system with tetracycline (TC)-grafted methoxy poly-(ethylene-glycol)‒poly-(D, L-lactic-co-glycolic acid) (mPEG‒PLGA) micelles (TC‒mPEG‒PLGA) with TC and mPEG‒PLGA for potential bone targeting. Prospectively, TC‒mPEG‒PLGA aims to deliver bioactive compounds, such as astragaloside IV (AS), for osteoporotic therapy. Preparation and evaluation of TC‒mPEG‒PLGA were accomplished via nano-properties, cytotoxicity, uptake by MC3T3-E1 cells, ability of hydroxyapatite targeting and potential bone targeting as well as pharmacodynamics in a rat model. The measured particle size of AS-loaded TC‒mPEG‒PLGA micelles was an average of 52.16 ± 2.44 nm, which exhibited a sustained release effect compared to that by free AS. The TC‒mPEG‒PLGA demonstrated low cytotoxicity and was easily taken by MC3T3-E1 cells. Through assaying of bone targeting and , we observed that TC‒mPEG‒PLGA could effectively increase AS accumulation in bone. A pharmacodynamics study in mice suggested potentially increased bone mineral density by AS-loaded TC‒mPEG‒PLGA in ovariectomized rats compared to that by free AS. The nano drug delivery system (TC‒mPEG‒PLGA) could target bone and , wherein it may be used as a novel delivery method for the enhancement of therapeutic effects of drugs with osteoporotic activity.
我们旨在创建一种纳米药物递送系统，该系统由接枝有四环素（TC）的甲氧基聚（乙二醇）-聚（D，L-乳酸-乙醇酸共聚物）（mPEG-PLGA）胶束（TC-mPEG-PLGA）组成，其中含有TC和mPEG-PLGA，具有潜在的骨靶向性。前瞻性地，TC-mPEG-PLGA旨在递送生物活性化合物，如黄芪甲苷IV（AS），用于骨质疏松症治疗。通过纳米特性、细胞毒性、MC3T3-E1细胞摄取、羟基磷灰石靶向能力和潜在骨靶向性以及大鼠模型中的药效学来完成TC-mPEG-PLGA的制备和评估。负载AS的TC-mPEG-PLGA胶束的测量粒径平均为52.16±2.44nm，与游离AS相比，表现出缓释效果。TC-mPEG-PLGA表现出低细胞毒性，并且易于被MC3T3-E1细胞摄取。通过骨靶向性测定，我们观察到TC-mPEG-PLGA可以有效增加AS在骨中的积累。小鼠药效学研究表明，与游离AS相比，负载AS的TC-mPEG-PLGA在去卵巢大鼠中可能增加骨矿物质密度。纳米药物递送系统（TC-mPEG-PLGA）可以靶向骨，并且其中它可以用作增强具有骨质疏松活性的药物治疗效果的新型递送方法。
