Subcutaneous long-acting release (LAR) formulations have been extensively developed in the clinic to increase patient compliance and reduce treatment cost. Despite preliminary success for some LAR systems, a major obstacle limiting the therapeutic effect remains on their interaction with surrounding tissues. In this review, we summarize how living bodies respond to injected or implanted materials, and highlight some typical strategies based on smart material design, which may significantly improve long-term subcutaneous drug delivery. Moreover, possible strategies to achieve ultra-long (months, years) subcutaneous drug delivery systems are proposed. Based on these discussions, we believe the well-designed subcutaneous long-acting formulations will hold great promise to improve patient quality of life in the clinic.

中文翻译：

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通过调节物质-生物环境的相互作用改善长期皮下给药。

皮下长效释放（LAR）制剂已在临床中得到广泛开发，以提高患者依从性并降低治疗成本。尽管某些LAR系统取得了初步的成功，但限制治疗效果的主要障碍仍然在于它们与周围组织的相互作用。在这篇综述中，我们总结了活体对注射或植入材料的反应，并重点介绍了基于智能材料设计的一些典型策略，这些策略可能会大大改善长期皮下药物的输送。此外，提出了实现超长（数月，数年）皮下给药系统的可能策略。基于这些讨论，我们认为设计良好的皮下长效制剂将有望改善临床患者的生活质量。