Investigation of the potential therapeutic effect of cationic lipoplex mediated fibroblast growth factor-2 encoding plasmid DNA delivery on wound healing.

Gülşah Erel-Akbaba, Hasan Akbaba
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引用次数: 4

Abstract

Background: Developing an alternative and efficient therapy for wound healing has been an important research topic for pharmaceutical sciences. A straightforward but effective system for delivering fibroblast growth factor-2 (FGF-2) encoding plasmid DNA (pFGF-2) for wound healing therapy was aimed to develop in this study.

Methods: In order to provide the delivery of pFGF-2, a delivery vector, namely, cationic lipid nanoparticle (cLN) was developed by the melt-emulsification process, complexed with pFGF-2 to form a lipoplex system and further characterized. The pFGF-2 binding and protecting ability of lipoplexes were evaluated. The cytotoxicity and transfection efficiency of the lipoplexes, FGF-2 expression levels, and in vitro wound healing ability have been investigated on the L929 fibroblast cell line.

Results: The obtained lipoplex system has a particle size of 88.53 nm with a low PDI (0.185), and zeta potential values of 27.8 mV with a spherical shape. The ability of cLNs to bind pFGF-2 and protect against nucleases was demonstrated by gel retardation assay. Furthermore, the developed FGF-2 carrying lipoplexes system showed significant transfection and FGF-2 expression ability comparing naked plasmid. Finally, scratch assay revealed that the developed system is able to promote in vitro cell proliferation/migration in 48 h.

Conclusion: Promising results have been achieved with the use of lipoplexes carrying pFGF-2, and this approach could be considered as a potentially applicable concept for the future gene-based wound healing therapies.

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阳离子脂质体介导的成纤维细胞生长因子-2编码质粒DNA递送对伤口愈合潜在治疗作用的研究。
背景:开发一种替代的、有效的伤口愈合疗法一直是制药科学的一个重要研究课题。本研究旨在开发一种直接而有效的系统,用于递送编码成纤维细胞生长因子-2 (FGF-2)的质粒DNA (pFGF-2),用于伤口愈合治疗。方法:为了提供pFGF-2的递送,采用熔融乳化法制备阳离子脂质纳米颗粒(cLN)作为递送载体,与pFGF-2络合形成脂质体体系并进一步表征。评价pFGF-2对脂质体的结合和保护能力。研究了脂丛的细胞毒性、转染效率、FGF-2表达水平及体外创面愈合能力。结果:获得的脂质体体系粒径为88.53 nm, PDI低(0.185),zeta电位值为27.8 mV,呈球形。通过凝胶阻滞实验证明了cLNs结合pFGF-2和保护核酸酶的能力。此外,与裸质粒相比,发育的携带FGF-2的脂丛系统具有显著的转染和FGF-2表达能力。最后,划痕实验显示,所开发的系统能够在48小时内促进体外细胞增殖/迁移。结论:使用携带pFGF-2的脂质体已经取得了令人鼓舞的结果,这种方法可以被认为是未来基于基因的伤口愈合治疗的潜在应用概念。
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