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用于伤口愈合应用的生物聚合物修饰多孔硅微粒的体外评估

In vitro assessment of biopolymer-modified porous silicon microparticles for wound healing applications.

作者信息

Mori Michela, Almeida Patrick V, Cola Michela, Anselmi Giulia, Mäkilä Ermei, Correia Alexandra, Salonen Jarno, Hirvonen Jouni, Caramella Carla, Santos Hélder A

机构信息

Department of Drug Sciences, University of Pavia, Italy.

Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland.

出版信息

Eur J Pharm Biopharm. 2014 Nov;88(3):635-42. doi: 10.1016/j.ejpb.2014.09.010. Epub 2014 Oct 8.

Abstract

The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications.

摘要

伤口愈合是一个非常复杂且动态的过程,旨在重新建立受损组织的完整性和功能。因此,迫切需要开发能够积极促进细胞增殖并重建细胞外基质的基于生物聚合物的复合材料。本研究的目的是制备并表征生物聚合物功能化的多孔硅(PSi)微粒,从而开发用于伤口愈合未来应用的药物递送微系统。热碳化PSi(THCPSi)微粒用壳聚糖以及硫酸软骨素/透明质酸的混合物进行包被,随后负载两种抗菌模型药物万古霉素和白藜芦醇。对改性PSi微粒的生物聚合物包被、载药程度和药物释放行为进行了体外评估。结果表明,THCPSi微粒的生物聚合物包被和载药均成功实现。此外,观察到两种测试药物均有持续释放。还评估了暴露于改性THCPSi微粒的成纤维细胞系的活力和增殖情况以及随后的活性氧(ROS)产生。细胞毒性和增殖结果表明,与未包被的微粒相比,不同浓度和时间点的生物聚合物包被的THCPSi微粒毒性较小。暴露于未包被和生物聚合物包被的PSi微粒的成纤维细胞产生的ROS表明,在测试浓度下,改性PSi微粒未诱导显著的ROS产生。总体而言,本研究中开发的基于生物聚合物的PSi微粒是用于伤口愈合应用的有前景的平台。

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