用于皮肤给药的重组人表皮生长因子脂质体和转移体:开发、表征和细胞毒性评估。

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-07-23 DOI:10.1002/ddr.22234
Yasaman Kiani Doustvaghe, Azadeh Haeri, Mahsa Mollapour Sisakht, Mohammad Amir Amirkhani, Hossein Vatanpour
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引用次数: 0

摘要

重组人表皮生长因子(rhEGF)作为一种抗衰老化合物被广泛用于伤口愈合治疗和美容。然而,由于经皮渗透性差和蛋白酶降解快,rhEGF 的局部用药治疗效果有限。为了克服这些障碍,本研究旨在开发含 rhEGF 的传统脂质体(rhEGF-CLs)和转移体(rhEGF-TFs),并对其进行表征,使其成为高效的皮肤载体。研究了纳米载体的粒度、ZP、形态、包封效率(EE%)、释放特性等理化特性,以及在人真皮成纤维细胞(HDF)和人胚胎肾(HEK293)细胞系中的体外细胞毒性。与对照组和游离 rhEGF 相比,rhEGF-TFs 具有理想的释放曲线、可接受的 EE%、最佳的细胞增殖性和最小的细胞毒性,因此被选为最佳配方,rhEGF-TFs 的浓度范围为 0.05 至 1.0 μg/mL。然而,较高的浓度会导致细胞活力下降。对于 rhEGF-TFs-2 而言,吐温 80 与脂质的比例为 20:80 最合适,其平均直径为 233.23 ± 2.64 nm,多分散指数为 0.33 ± 0.05,ZP 为 -15.46 ± 0.29 mV,EE% 为 60.50 ± 1.91。这些配方在 5°C 温度下至少可保持稳定 1 个月。TEM 和 SEM 显微镜显示,rhEGF-TFs-2 具有规则的形状和单纤毛结构。体外药物释放研究证实了 rhEGF-TFs-2 的优越性,24 小时内 rhEGF 的最佳累积释放量约为 82%;弗朗兹扩散细胞研究显示,与游离 rhEGF 溶液相比,rhEGF-TFs-2 的皮肤渗透率更高。综上所述,我们认为 rhEGF-TFs 可用作伤口愈合和皮肤再生产品的理想配方。
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Recombinant human epidermal growth factor-loaded liposomes and transferosomes for dermal delivery: Development, characterization, and cytotoxicity evaluation

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.

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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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