College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, PR China.
Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, PR China.
J Control Release. 2021 Oct 10;338:486-504. doi: 10.1016/j.jconrel.2021.08.056. Epub 2021 Sep 2.
Bone is a connective tissue that support the entire body and protect the internal organs. However, there are great challenges on curing intractable skeletal diseases such as hypercalcemia, osteoporosis and osteoarthritis. To address these issues, calcitonin (CT) therapy is an effective treatment alternative to regulate calcium metabolism and suppress inflammation response, which are closely related to skeletal diseases. Traditional calcitonin formulation requires frequent administration due to the low bioavailability resulting from the short half-life and abundant calcitonin receptors distributed through the whole body. Therefore, long-term and targeted calcitonin delivery systems (LCDS and TCDS) have been widely explored as the popular strategies to overcome the intrinsic limitations of calcitonin and improve the functions of calcium management and inflammation inhibition in recent years. In this review, we first explain the physiological effects of calcitonin on bone remodeling: (i) inhibitory effects on osteoclasts and (ii) facilitated effects on osteoblasts. Then we summarized four strategies for spatiotemporally controlled delivery of calcitonin: micro-/nanomedicine (e.g. inorganic micro-/nanomedicine, polymeric micro-/nanomedicine and supramolecular assemblies), hydrogels (especially thermosensitive hydrogels), prodrug (PEGylation and targeting design) and hybrid biomaterials. Subsequently, we discussed the application of LCDS and TCDS in treating hypercalcemia, osteoporosis, and arthritis. Understanding and analyzing these advanced calcitonin delivery applications are essential for future development of calcitonin therapies toward skeletal diseases with superior efficacy in clinic.
骨骼是一种结缔组织，支撑着整个身体并保护内部器官。然而，治疗诸如高钙血症、骨质疏松症和骨关节炎等棘手骨骼疾病仍存在巨大挑战。为了解决这些问题，降钙素（CT）疗法是一种有效的治疗选择，可以调节钙代谢和抑制炎症反应，而这些与骨骼疾病密切相关。由于半衰期短且全身分布丰富的降钙素受体，传统的降钙素制剂的生物利用度较低，因此需要频繁给药。因此，近年来，长效和靶向降钙素递送系统（LCDS 和 TCDS）已被广泛探索，作为克服降钙素内在局限性和改善钙管理和炎症抑制功能的流行策略。在这篇综述中，我们首先解释了降钙素对骨骼重塑的生理作用：（i）对破骨细胞的抑制作用和（ii）对成骨细胞的促进作用。然后，我们总结了降钙素时空控制递送的四种策略：微/纳米医学（例如无机微/纳米医学、聚合物微/纳米医学和超分子组装）、水凝胶（特别是热敏水凝胶）、前药（PEG 化和靶向设计）和混合生物材料。随后，我们讨论了 LCDS 和 TCDS 在治疗高钙血症、骨质疏松症和关节炎中的应用。了解和分析这些先进的降钙素递送应用对于未来开发治疗骨骼疾病的降钙素疗法具有优越的临床疗效至关重要。
