An Intelligent Transdermal Formulation of ALA‐Loaded Copolymer Thermogel with Spontaneous Asymmetry by Using Temperature‐Induced Sol–Gel Transition and Gel–Sol (Suspension) Transition on Different Sides

作者：Dinglingge Cao, Xi Chen, Feng Cao, Wen Guo, Jingyu Tang, Caiyun Cai, Shuquan Cui, Xiaowei Yang, Lin Yu, Yong Su, Jiandong Ding · 发表于：Advanced Functional Materials · 年份：2021 · DOI：10.1002/adfm.202100349 · 被引用次数：68 · 研究领域：Hydrogels: synthesis, properties, applications、Photodynamic Therapy Research Studies、Advanced Drug Delivery Systems

Abstract Aqueous solutions of some amphiphilic block copolymers undergo a sol–gel transition upon heating and are thus called thermogels. In the thermogel family, some systems also exhibit a gel–sol (suspension) transition at higher temperatures following the sol–gel transition, which is usually ignored in biomedical applications. Herein, for the first time, a case is reported employing both the sol–gel transition and the gel–sol (suspension) transition, which is found in the development of a transdermal hydrogel formulation containing 5‐aminolevulinic acid for photodynamic therapy (PDT) of skin disease. Two poly( d , l ‐lactide‐ co ‐glycolide)‐ b ‐poly(ethylene glycol)‐ b ‐poly( d , l ‐lactide‐ co ‐glycolide) triblock copolymers of different block lengths are synthesized. The transition temperatures of the formulation can be easily adjusted to meet the condition of sol–gel transition temperature ( T gel ) < room temperature ( T air ) < gel–sol (suspension) temperature ( T sol (suspension) ) < body temperature ( T body ) via changing the blending ratio. Therefore, after applying to skin, formulation of spontaneous asymmetry with a hydrogel outside and a sol (suspension) inside can avoid free flowing and achieve rapid release to ensure an efficient PDT. This study demonstrates such a concept via characterizations of the “block blend” biomaterials and drug release profiles, and also via cell experiments, in vitro permeation, and in vivo transdermal delivery studies.