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Dual-action of thermoresponsive gels containing DsiRNA-loaded gold nanoparticles for diabetic wound therapy: Characterization, in vitro safety and healing efficacy
Saudi Pharmaceutical Journal ( IF 3.0 ) Pub Date : 2020-09-18 , DOI: 10.1016/j.jsps.2020.09.007
Ahmad Yasser Hamdi Nor Azlan , Haliza Katas , Nur Hamizah Habideen , Mohd Fauzi Mh Busra

Diabetic wounds are difficult to treat due to multiple causes, including reduced blood flow and bacterial infections. Reduced blood flow is associated with overexpression of prostaglandin transporter (PGT) gene, induced by hyperglycaemia which causing poor vascularization and healing of the wound. Recently, gold nanoparticles (AuNPs) have been biosynthesized using cold and hot sclerotium of Lignosus rhinocerotis extracts (CLRE and HLRE, respectively) and capped with chitosan (CS) to produce biocompatible antibacterial nanocomposites. The AuNPs have shown to produce biostatic effects against selected gram positive and negative bacteria. Therefore, in this study, a dual therapy for diabetic wound consisting Dicer subtract small interfering RNA (DsiRNA) and AuNPs was developed to improve vascularization by inhibiting PGT gene expression and preventing bacterial infection, respectively. The nanocomposites were incorporated into thermoresponsive gel, made of pluronic and polyethylene glycol. The particle size of AuNPs synthesized using CLRE (AuNPs-CLRE) and HLRE (AuNPs-HLRE) was 202 ± 49 and 190 ± 31 nm, respectively with positive surface charge (+30 to + 45 mV). The thermoresponsive gels containing DsiRNA-AuNPs gelled at 32 ± 1 °C and released the active agents in sufficient amount with good texture and rheological profiles for topical application. DsiRNA-AuNPs and those incorporated into thermoresponsive pluronic gels demonstrated high cell viability, proliferation and cell migration rate via in vitro cultured cells of human dermal fibroblasts, indicating their non-cytotoxicity and wound healing properties. Taken together, the thermoresponsive gels are expected to be useful as a potential dressing that promotes healing of diabetic wounds.



中文翻译:

载有DsiRNA的金纳米颗粒的热响应性凝胶对糖尿病伤口治疗的双重作用:表征,体外安全性和治愈功效

糖尿病伤口由于多种原因而难以治疗,包括血流量减少和细菌感染。血流量减少与高血糖症引起的前列腺素转运蛋白(PGT)基因的过表达有关,高血糖症导致血管形成不良和伤口愈合。近来,金纳米颗粒(AuNPs)已被利用木犀牛的冷和热菌核生物合成。提取物(分别为CLRE和HLRE),并用壳聚糖(CS)封端以产生生物相容的抗菌纳米复合材料。AuNP已显示出对选定的革兰氏阳性和阴性细菌产生生物抑制作用。因此,在这项研究中,开发了一种由Dicer减去小干扰RNA(DsiRNA)和AuNPs组成的糖尿病伤口双重疗法,分别通过抑制PGT基因表达和预防细菌感染来改善血管形成。将纳米复合材料掺入由普鲁尼克和聚乙二醇制成的热敏凝胶中。使用CLRE(AuNPs-CLRE)和HLRE(AuNPs-HLRE)合成的AuNPs的粒径分别为202±49和190±31 nm,具有正表面电荷(+30至+ 45 mV)。含有DsiRNA-AuNPs的热敏凝胶在32±1°C的温度下胶凝,并释放出足够量的活性剂,具有良好的质地和流变性,可局部使用。DsiRNA-AuNPs和掺入热响应性普鲁尼克凝胶的DsiRNA-AuNPs具有高细胞活力,增殖能力和通过人真皮成纤维细胞的体外培养细胞,表明其无细胞毒性和伤口愈合特性。综上所述,热敏性凝胶有望用作促进糖尿病伤口愈合的潜在敷料。

更新日期:2020-11-17
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