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Pharmaceutical evaluation of atorvastatin-loaded nanostructured lipid carriers incorporated into the gelatin/hyaluronic acid/polycaprolactone scaffold for the skin tissue engineering
Journal of Biomaterials Applications ( IF 2.9 ) Pub Date : 2020-11-04 , DOI: 10.1177/0885328220970760
Mahsa Ahmadi 1 , Mehdi Mehdikhani 1 , Jaleh Varshosaz 2 , Shadi Farsaei 3 , Hadis Torabi 4
Affiliation  

In this study, gelatin/hyaluronic acid (HA) scaffolds containing different amounts of atorvastatin-loaded nanostructured lipid carriers (NLCs) coated entirely with polycaprolactone (PCL) film were fabricated for skin regeneration. 12 atorvastatin-loaded NLCs formulations were synthesized, and particle size, zeta potential, drug entrapment efficiency (EE), and drug release of the formulations were determined. The optimum freeze-dried atorvastatin-loaded NLCs were added in 3 different weight percentages to the gelatin and HA membranous scaffolds. Thereafter, the membranes were coated entirely by a thin layer of the PCL. They were characterized, and then mechanical properties, in vitro degradation and in vitro drug release were assessed. Moreover, human dermal fibroblasts (HDF) were cultured on the prepared nanocomposite scaffolds in order to investigate the cytotoxicity by the MTT assay after the first day, third day, and fifth day. Results revealed that the most favorable atorvastatin-loaded NLCs had 99.54 nm average particle size, −24.30 mV zeta potential, 97.98% EE, and 75.24% drug release within 237 hrs. Mechanical tests indicated that all the three scaffolds had approximately a 90 MPa elastic modulus which was more than two-fold of tensile modulus of normal human skin. The in vitro degradation test demonstrated that the membranes were degraded up to 98% after 5 days, and the scaffolds drug release efficiency (DRE) was in a range of 75–79% during those 5 days. The MTT assay results confirmed the cytocompatibility of the scaffolds. The scaffold containing 54.1 wt% NCLs was the optimum sample (S3). Scanning Electron Microscopy (SEM) images of the latter one showed the uniform distribution of the NLCs with an average size of 150 nm, and the images of cultured HDF illustrated the good cell attachment. In conclusion, suitable physicochemical and biological properties of the novel gelatin/HA/PCL nanocomposite scaffold containing 54.1 wt% atorvastatin-loaded NLCs (S3) can be a good candidate for skin regeneration.



中文翻译:

用于皮肤组织工程的明胶/透明质酸/聚己内酯支架中负载阿托伐他汀的纳米结构脂质载体的药物评价

在这项研究中,制造了含有不同数量的阿托伐他汀负载纳米结构脂质载体 (NLC) 的明胶/透明质酸 (HA) 支架,该载体完全涂有聚己内酯 (PCL) 薄膜,用于皮肤再生。合成了 12 个载有阿托伐他汀的 NLC 制剂,并测定了制剂的粒径、zeta 电位、药物包封率 (EE) 和药物释放。将 3 种不同重量百分比的最佳冷冻干燥阿托伐他汀 NLC 添加到明胶和 HA 膜支架中。此后,膜完全被一层薄薄的 PCL 覆盖。对其进行表征,然后评估机械性能、体外降解和体外药物释放。而且,在制备的纳米复合材料支架上培养人真皮成纤维细胞 (HDF),以在第一天、第三天和第五天后通过 MTT 测定研究细胞毒性。结果显示,最有利的负载阿托伐他汀的 NLC 在 237 小时内具有 99.54 nm 平均粒径、-24.30 mV zeta 电位、97.98% EE 和 75.24% 药物释放。力学测试表明,所有三种支架的弹性模量均约为 90 MPa,是正常人体皮肤拉伸模量的两倍多。体外降解试验表明,膜在 5 天后降解高达 98%,在这 5 天内支架药物释放效率(DRE)在 75-79% 的范围内。MTT测定结果证实了支架的细胞相容性。包含 54 的脚手架。3)。后者的扫描电子显微镜 (SEM) 图像显示 NLC 分布均匀,平均尺寸为 150 nm,培养的 HDF 图像显示了良好的细胞附着。总之,含有 54.1 wt% 的阿托伐他汀 NLC (S 3 ) 的新型明胶/HA/PCL 纳米复合支架的合适物理化学和生物学特性可以成为皮肤再生的良好候选者。

更新日期:2020-11-06
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