Bakhrushina Elena O, Titova Svetlana A, Sakharova Polina S, Plakhotnaya Olga N, Grikh Viktoriya V, Patalova Alla R, Gorbacheva Anna V, Krasnyuk Ivan I, Krasnyuk Ivan I
I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia.
Pharmaceutics. 2025 Jun 6;17(6):750. doi: 10.3390/pharmaceutics17060750.
Stimuli-sensitive (in situ) drug delivery systems are a dynamically developing area of pharmaceutical research. Over the past decade, the number of studies on such systems has doubled. Among these, phase-inversion (or phase-sensitive) formulations, which were among the earliest proposed, offer significant advantages, including enhanced stability and stimuli-responsiveness. However, phase-inversion systems have remained relatively understudied. Despite the existence of three patented technologies (Atrigel, BEPO, FluidCrystal) for delivery systems utilizing phase inversion for various routes of administration, the absence of unified approaches to development and standardization has significantly impeded the introduction of novel, effective drugs into clinical practice. This review examined the main polymers and solvents used to create phase-inversion compositions and discussed the feasibility of introducing other excipients to modify the systems' physicochemical properties. The most commonly used polymers included polylactide-co-glycolide, shellac, and polylactic acid. The most frequently used solvents were -methylpyrrolidone and dimethyl sulfoxide. Following an analysis of clinical studies of phase-sensitive drugs conducted over the past 25 years, as well as original research indexed in PubMed, ScienceDirect, and Google Scholar, the main problems hindering the broader adoption of phase-inversion systems in clinical practice were identified, and recommendations for further development in this promising area were provided.
刺激敏感（原位）药物递送系统是药物研究中一个动态发展的领域。在过去十年中，关于此类系统的研究数量翻了一番。其中，最早提出的相转变（或相敏感）制剂具有显著优势，包括增强的稳定性和刺激响应性。然而，相转变系统的研究相对较少。尽管存在三种利用相转变用于各种给药途径的递送系统的专利技术（Atrigel、BEPO、FluidCrystal），但缺乏统一的开发方法和标准化严重阻碍了新型有效药物引入临床实践。本综述研究了用于制备相转变组合物的主要聚合物和溶剂，并讨论了引入其他辅料以改变系统物理化学性质的可行性。最常用的聚合物包括聚乳酸-乙醇酸共聚物、虫胶和聚乳酸。最常用的溶剂是N-甲基吡咯烷酮和二甲基亚砜。在分析过去25年进行的相敏感药物临床研究以及PubMed、ScienceDirect和谷歌学术搜索中索引的原始研究后，确定了阻碍相转变系统在临床实践中更广泛应用的主要问题，并为这一有前景的领域的进一步发展提供了建议。
