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通过超临界发泡与热致孔剂浸出相结合的方法对具有可调大孔隙率的载药聚(ε-己内酯)支架进行无溶剂加工

Solvent-Free Processing of Drug-Loaded Poly(ε-Caprolactone) Scaffolds with Tunable Macroporosity by Combination of Supercritical Foaming and Thermal Porogen Leaching.

作者信息

Santos-Rosales Víctor, Ardao Inés, Goimil Leticia, Gomez-Amoza Jose Luis, García-González Carlos A

机构信息

Department of Pharmacology, Pharmacy and Pharmaceutical Technology, I + D Farma Group (GI-1645), Faculty of Pharmacy and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.

BioFarma Research Group, Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CiMUS), Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.

出版信息

Polymers (Basel). 2021 Jan 4;13(1):159. doi: 10.3390/polym13010159.

DOI:10.3390/polym13010159
PMID:33406680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7795801/
Abstract

Demand of scaffolds for hard tissue repair increases due to a higher incidence of fractures related to accidents and bone-diseases that are linked to the ageing of the population. Namely, scaffolds loaded with bioactive agents can facilitate the bone repair by favoring the bone integration and avoiding post-grafting complications. Supercritical (sc-)foaming technology emerges as a unique solvent-free approach for the processing of drug-loadenu7d scaffolds at high incorporation yields. In this work, medicated poly(ε-caprolactone) (PCL) scaffolds were prepared by sc-foaming coupled with a leaching process to overcome problems of pore size tuning of the sc-foaming technique. The removal of the solid porogen (BA, ammonium bicarbonate) was carried out by a thermal leaching taking place at 37 °C and in the absence of solvents for the first time. Macroporous scaffolds with dual porosity (50-100 µm and 200-400 µm ranges) were obtained and with a porous structure directly dependent on the porogen content used. The processing of ketoprofen-loaded scaffolds using BA porogen resulted in drug loading yields close to 100% and influenced its release profile from the PCL matrix to a relevant clinical scenario. A novel solvent-free strategy has been set to integrate the incorporation of solid porogens in the sc-foaming of medicated scaffolds.

摘要

由于与事故相关的骨折以及与人口老龄化相关的骨疾病发病率上升,对用于硬组织修复的支架的需求增加。具体而言,负载生物活性剂的支架可以通过促进骨整合和避免移植后并发症来促进骨修复。超临界(sc-)发泡技术作为一种独特的无溶剂方法出现,可用于以高掺入率加工载药支架。在这项工作中,通过sc-发泡结合浸出工艺制备了含药聚(ε-己内酯)(PCL)支架,以克服sc-发泡技术的孔径调节问题。首次在37°C且无溶剂的条件下通过热浸出来去除固体致孔剂(BA,碳酸氢铵)。获得了具有双重孔隙率(50-100μm和200-400μm范围)的大孔支架,其多孔结构直接取决于所用致孔剂的含量。使用BA致孔剂加工载有酮洛芬的支架导致药物负载率接近100%,并在相关临床情况下影响其从PCL基质中的释放曲线。已经制定了一种新颖的无溶剂策略,以将固体致孔剂的掺入整合到含药支架的sc-发泡中。

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