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用于皮肤再生的介孔二氧化硅负载聚己内酯-壳聚糖混合膜

Mesoporous Silica-Loaded PCL-CHT Hybrid Membranes for Skin Regeneration.

作者信息

Salerno Simona, Morelli Sabrina, Vardè Andrea, De Santo Marzia, Longobucco Camilla, Spadafora Angelica, Dell'olio Gianluca, Giordano Francesca, Morelli Catia, Leggio Antonella, Pasqua Luigi, De Bartolo Loredana

机构信息

Institute on Membrane Technology, National Research Council of Italy, ITM-CNR, via P. Bucci, cubo 17/C, Rende, CS I-87036, Italy.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, via P. Bucci, Rende, CS 87036, Italy.

出版信息

ACS Appl Mater Interfaces. 2025 Aug 20;17(33):46651-46666. doi: 10.1021/acsami.5c09164. Epub 2025 Aug 10.

DOI:10.1021/acsami.5c09164
PMID:40785071
Abstract

An innovative multifunctional membrane, combining polymeric materials with inorganic nanoparticles and bioactive molecules, was developed for skin tissue application. The strategy was to synthesize a hybrid polymeric/silica membrane in which SiO nanoparticles are dispersed inside the membrane matrix. To this end, hexagonal calcined mesoporous silica nanoparticles (MSNs) with a uniform structure, 187.6 ± 4.6 nm diameter, and 5.1 nm pore size were synthesized to accommodate molecules of pharmaceutical interest in the silica mesopores. MSNs were then loaded with daidzein, a prominent isoflavone well-known for its anti-inflammatory, antioxidant, and antidiabetic activity, through chemical-physical interactions to investigate its role as a drug carrier. The hybrid membranes were created by combining chitosan (CHT) and polycaprolactone (PCL) polymers with mesoporous silica nanoparticles, optimizing the polymer-to-silica molar ratio up to 5:1, for which enhanced hydrophilicity (WCA = 55.5 ± 2.9°), moisture permeability (WVTR = 32.2 ± 4.4 g/m·h), and swelling capacity (68 ± 11%) were achieved. Drug release studies on the hybrid membrane incorporating daidzein-preloaded silica confirmed sustained delivery of the active compound, releasing 88.9 ± 0.9 μM/cm after 48 hours. The physical-chemical and morphological-structural properties of the membranes favored the adhesion and growth of human keratinocytes, providing biomimetic cues to facilitate epidermal maturation. In the developed epidermal models, oxygen consumption, which is representative of an active cellular metabolic state, rises over time, leveling off at day 7. The highest oxygen uptake activity was observed in the hybrid membrane PCL-CHT/MSN, achieving values of 161 ± 3 μmol/L at day 11. Hybrid epidermal-membrane constructs enhance keratinocyte proliferation and differentiation, as evidenced by specific cytokeratins, matrix metalloproteinases, and cyclin D1 expression, suggesting improved stratification and epidermal remodeling.

摘要

开发了一种创新的多功能膜,它将聚合物材料与无机纳米颗粒和生物活性分子相结合,用于皮肤组织应用。其策略是合成一种杂化聚合物/二氧化硅膜,其中SiO纳米颗粒分散在膜基质内部。为此,合成了具有均匀结构、直径为187.6±4.6 nm且孔径为5.1 nm的六方煅烧介孔二氧化硅纳米颗粒(MSN),以在二氧化硅介孔中容纳具有药物活性的分子。然后通过化学物理相互作用将大豆苷元(一种以其抗炎、抗氧化和抗糖尿病活性而闻名的著名异黄酮)负载到MSN上,以研究其作为药物载体的作用。通过将壳聚糖(CHT)和聚己内酯(PCL)聚合物与介孔二氧化硅纳米颗粒结合来制备杂化膜,将聚合物与二氧化硅的摩尔比优化至5:1,由此实现了增强的亲水性(水接触角WCA = 55.5±2.9°)、透湿性(水蒸气透过率WVTR = 32.2±4.4 g/m·h)和溶胀能力(68±11%)。对载有预负载大豆苷元的二氧化硅的杂化膜进行的药物释放研究证实了活性化合物的持续释放,48小时后释放量为88.9±0.9 μM/cm²。膜的物理化学和形态结构特性有利于人角质形成细胞的黏附和生长,提供仿生线索以促进表皮成熟。在开发的表皮模型中,代表活跃细胞代谢状态的耗氧量随时间增加,在第7天趋于平稳。在杂化膜PCL-CHT/MSN中观察到最高的氧摄取活性,在第11天达到161±3 μmol/L的值。杂化表皮膜构建体增强了角质形成细胞的增殖和分化,这通过特定细胞角蛋白、基质金属蛋白酶和细胞周期蛋白D1的表达得到证明,表明分层和表皮重塑得到改善。

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