Sha Zhuomin, Wu Yongjia, Zheng Yi, Yang Ke, Gong Xinyi, Xuan Lu, Li Xiang, Chen Xuepeng
School of Stomatology, The Affiliated Hospital of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, and Cancer Center of Zhejiang University, Hangzhou, China.
Shaoxing Stomatological Hospital, Shaoxing, China.
Drug Deliv. 2025 Dec;32(1):2522109. doi: 10.1080/10717544.2025.2522109. Epub 2025 Jun 27.
Periodontitis is a prevalent and destructive inflammatory disease that is closely linked to various systemic conditions. In recent years, the local delivery of therapeutic agents via novel biomaterials has emerged as a promising strategy for periodontitis therapy. Notably, the pathological reduction of endogenous power of hydrogen (pH) within periodontal pockets provides a valuable trigger for stimuli-responsive drug delivery. This narrative review aims to summarize advances in endogenous pH-responsive drug delivery systems (DDS) for periodontitis treatment, with a focus on their design mechanisms and therapeutic potential. A comprehensive literature search was conducted in PubMed/Medline, Web of Science, Scopus, and Embase (up to March 2025) using keywords 'pH-responsive', 'drug delivery', and 'periodontitis'. Studies investigating the preparation and therapeutic effects of pH-responsive DDS for periodontitis were included and critically evaluated. pH-responsive materials are capable of undergoing structural transformations and triggering drug release in the pathological acidic microenvironment of periodontitis. The DDS based on these materials can be broadly classified into three categories: nanoparticles, nanofibers, and hydrogels. The protonation and the cleavage of chemical bonds are the primary response mechanisms. Programmed periodontitis recovery is crucial in the design of these DDS. pH-responsive DDS offer a promising strategy for localized periodontal therapy. However, challenges such as clinical translation, biosafety evaluation, and personalized release modulation remain. Future research should focus on multifunctional, programmable platforms to accelerate clinical adoption.
牙周炎是一种常见的破坏性炎症性疾病，与多种全身疾病密切相关。近年来，通过新型生物材料局部递送治疗剂已成为牙周炎治疗的一种有前景的策略。值得注意的是，牙周袋内源性氢（pH）的病理性降低为刺激响应性药物递送提供了有价值的触发因素。这篇叙述性综述旨在总结用于牙周炎治疗的内源性pH响应性药物递送系统（DDS）的进展，重点关注其设计机制和治疗潜力。使用关键词“pH响应”、“药物递送”和“牙周炎”在PubMed/Medline、Web of Science、Scopus和Embase（截至2025年3月）上进行了全面的文献检索。纳入并严格评估了研究pH响应性DDS用于牙周炎的制备和治疗效果的研究。pH响应性材料能够在牙周炎的病理性酸性微环境中发生结构转变并触发药物释放。基于这些材料的DDS可大致分为三类：纳米颗粒、纳米纤维和水凝胶。化学键的质子化和断裂是主要的响应机制。在这些DDS的设计中，程序性牙周炎恢复至关重要。pH响应性DDS为局部牙周治疗提供了一种有前景的策略。然而，临床转化、生物安全性评估和个性化释放调节等挑战仍然存在。未来的研究应专注于多功能、可编程平台，以加速临床应用。
