Department of Biomedical Engineering, Faculty of Engineering, University of Isfahan, Isfahan, Islamic Republic of Iran.
Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran.
J Biomater Appl. 2021 Mar;35(8):958-977. doi: 10.1177/0885328220970760. Epub 2020 Nov 4.
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 (S). 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 (S) can be a good candidate for skin regeneration.
在这项研究中，制备了一种含有不同载药量阿托伐他汀的纳米结构脂质载药（NLC）的明胶/透明质酸（HA）支架，并用聚己内酯（PCL）薄膜完全包裹。合成了 12 种载药 NLC 制剂，测定了制剂的粒径、Zeta 电位、药物包封效率（EE）和药物释放。选择最优的载药 NLC 冻干粉以 3 种不同的重量百分比添加到明胶和 HA 膜支架中。然后，用一层薄薄的 PCL 完全包裹膜。对其进行了表征，然后评估了机械性能、体外降解和体外药物释放。此外，将人真皮成纤维细胞（HDF）培养在制备好的纳米复合材料支架上，通过 MTT 试验在第 1 天、第 3 天和第 5 天检测细胞毒性。结果表明，最有利的载药 NLC 的平均粒径为 99.54nm，Zeta 电位为-24.30mV，EE 为 97.98%，在 237 小时内药物释放率为 75.24%。力学试验表明，所有三种支架的弹性模量约为 90MPa，是正常人体皮肤拉伸模量的两倍多。体外降解试验表明，5 天后膜降解率高达 98%，5 天内支架药物释放效率（DRE）在 75%-79%之间。MTT 试验结果证实了支架的细胞相容性。载药量为 54.1wt%的 NCL 支架（S）为最佳样本。后者的扫描电子显微镜（SEM）图像显示 NLC 分布均匀，平均粒径为 150nm，培养的 HDF 图像显示出良好的细胞附着。总之，新型明胶/HA/PCL 纳米复合材料支架具有合适的理化和生物学性能，含有 54.1wt%载药量的阿托伐他汀的 NLC（S）支架可以成为皮肤再生的良好候选材料。
