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载有人重组表皮生长因子的脂质体和传递体经皮给药系统的研究:制备、表征和细胞毒性评价。

Recombinant human epidermal growth factor-loaded liposomes and transferosomes for dermal delivery: Development, characterization, and cytotoxicity evaluation.

机构信息

Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Drug Dev Res. 2024 Aug;85(5):e22234. doi: 10.1002/ddr.22234.

DOI:10.1002/ddr.22234
PMID:39041350
Abstract

Recombinant human epidermal growth factor (rhEGF) is widely utilized as an antiaging compound in wound-healing therapies and cosmetic purposes. However, topical administration of rhEGF has limited treatment outcomes because of its poor percutaneous penetration and rapid proteinase degradation. To overcome these obstacles, this study aims to develop and characterize rhEGF-containing conventional liposomes (rhEGF-CLs) and transferosomes (rhEGF-TFs) as efficient dermal carriers. Physicochemical characterization such as particle size, zeta potential (ZP), morphology, encapsulation efficiency (EE%), and release properties of nanocarriers as well as in vitro cytotoxicity in human dermal fibroblast (HDF) and human embryonic kidney (HEK293) cell lines were investigated. rhEGF-TFs at the rhEGF concentration ranging from 0.05 to 1.0 μg/mL were chosen as the optimum formulation due to the desired release profile, acceptable EE%, optimal cell proliferation, and minimal cytotoxicity compared to the control and free rhEGF. However, higher concentrations caused a decrease in cell viability. The ratio 20:80 of Tween 80 to lipid was optimal for rhEGF-TFs-2, which had an average diameter of 233.23 ± 2.64 nm, polydispersity index of 0.33 ± 0.05, ZP of -15.46 ± 0.29 mV, and EE% of 60.50 ± 1.91. The formulations remained stable at 5°C for at least 1 month. TEM and SEM microscopy revealed that rhEGF-TFs-2 had a regular shape and unilamellar structure. In vitro drug release studies confirmed the superiority of rhEGF-TFs-2 in terms of optimal cumulative release of rhEGF approximately 82% within 24 h. Franz diffusion cell study showed higher rhEGF-TFs-2 skin permeation compared to free rhEGF solution. Taken together, we concluded that rhEGF-TFs can be used as a promising formulation for wound healing and skin regeneration products.

摘要

重组人表皮生长因子(rhEGF)广泛用作伤口愈合疗法和美容目的的抗衰老化合物。然而,由于其经皮渗透能力差和蛋白酶快速降解,rhEGF 的局部给药治疗效果有限。为了克服这些障碍,本研究旨在开发和表征含 rhEGF 的常规脂质体(rhEGF-CLs)和传递体(rhEGF-TFs)作为有效的皮肤载体。研究了纳米载体的物理化学特性,如粒径、Zeta 电位(ZP)、形态、包封效率(EE%)和释放特性,以及在人真皮成纤维细胞(HDF)和人胚肾(HEK293)细胞系中的体外细胞毒性。rhEGF-TFs 在 rhEGF 浓度范围为 0.05 至 1.0μg/mL 时被选为最佳配方,因为与对照和游离 rhEGF 相比,它具有理想的释放曲线、可接受的 EE%、最佳的细胞增殖和最小的细胞毒性。然而,更高的浓度会导致细胞活力下降。对于 rhEGF-TFs-2,Tween 80 与脂质的比例为 20:80 是最佳的,其平均直径为 233.23±2.64nm,多分散指数为 0.33±0.05,ZP 为-15.46±0.29mV,EE%为 60.50±1.91。制剂在 5°C 下至少稳定 1 个月。TEM 和 SEM 显微镜显示,rhEGF-TFs-2 具有规则的形状和单分子层结构。体外药物释放研究证实了 rhEGF-TFs-2 的优越性,即在 24 小时内rhEGF 的累积释放量约为 82%。Franz 扩散细胞研究表明,rhEGF-TFs-2 的皮肤渗透能力高于游离 rhEGF 溶液。综上所述,我们得出结论,rhEGF-TFs 可以用作伤口愈合和皮肤再生产品的有前途的制剂。

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