Recombinant human parathyroid hormone 1-34 (rhPTH 1-34) is the most potent anabolic drug recommended for patients with osteoporosis who do not respond to conventional treatment. However, subcutaneous intermittent injection is the only effective regimen due to its unusual action of mechanism. This regimen is inconvenient and is a big hurdle in clinical applications. In this study, we designed polyelectrolyte microbeads that can deliver rhPTH 1-34 in response to Ca²⁺ concentration, which indicates the osteoporotic status. Dextran photopolymer was synthesized, mixed with anionic monoacrylate, and photopolymerized by passing through capillary microfluidics to obtain the microbeads. The anionic property of microbeads was confirmed by toluidine blue staining. One microbead, loaded with a 1 day dose of rhPTH 1-34 (23.4 ± 0.9 μg), released rhPTH 1-34 in a triggered manner following the addition of Ca²⁺ ion. In vitro cell study demonstrated that rhPTH 1-34 released in a pulsatile manner from the microbeads induced osteogenic markers (ALP, RUNX2, and OPN) and precipitated mineral disposition more effectively.

中文翻译：

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钙触发微珠中甲状旁腺激素的脉冲递送，用于骨质疏松症的治疗

重组人甲状旁腺激素1-34（rhPTH 1-34）是推荐用于对常规治疗无反应的骨质疏松症患者的最有效的合成代谢药物。然而，由于其异常的机制作用，皮下间歇注射是唯一有效的方案。该方案不方便并且在临床应用中是一个很大的障碍。在这项研究中，我们设计了聚电解质微珠，可以响应Ca ²⁺传递rhPTH 1-34浓度，表明骨质疏松状态。合成葡聚糖光聚合物，与阴离子单丙烯酸酯混合，并通过毛细管微流体进行光聚合以获得微珠。通过甲苯胺蓝染色证实了微珠的阴离子性质。装有1天剂量的rhPTH 1-34（23.4±0.9μg）的一个微珠在添加Ca ²⁺离子后以触​​发方式释放rhPTH 1-34 。体外细胞研究表明，从微珠中以脉动方式释放的rhPTH 1-34可以诱导成骨标记（ALP，RUNX2和OPN）并更有效地沉淀矿物质。