Gold Nanoparticles for Enhanced Skin Permeation of a Protein Drug

Kanokwan Singpanna, Chaiyakarn Pornpitchanarong, Prasopchai Patrojanasophon, Theerasak Rojanarata, Tanasait Ngawhirunpat, Boonnada Pamornpathomkul, Praneet Opanasopit
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Abstract

Abstract This study aimed to evaluate the effect of gold nanoparticles (AuNPs) stabilized by citrate ions (Ci-AuNPs) and chitosan (CS-AuNPs) on skin permeation of a protein drug, albumin-fluorescein isothiocyanate conjugate (FITC-BSA). Ci-AuNPs and CS-AuNPs were prepared by the Turkevich method and microwave-assisted method, respectively. The particle size, surface charge, and morphology of the AuNPs were investigated. The skin permeation study through the porcine skin, skin permeation pathway, and the safety of the AuNPs were examined using vertical Franz diffusion cells, confocal laser scanning microscopy (CLSM), and MTT assay, respectively. AuNPs had a spherical shape with size ranging in a nano-scale (<100 nm). Ci-AuNPs exhibited negatively charged surfaces, while CS-AuNPs were positive. A co-delivery of FITC-BSA with CS-AuNPs showed approximately 3.5-fold greater permeability than the FITC-BSA alone. Interestingly, no significant improvement was observed from Ci-AuNPs co-delivery. The CLSM visualization suggested that the delivery of the model protein was enhanced through the transepidermal pathway. Furthermore, the CS-AuNPs presented no significant cytotoxicity toward normal human fibroblasts. Above all, the developed CS-AuNPs were proposed to be safe and effective nanosystem as a skin permeation enhancer for the transdermal delivery of proteins. Keywords: Gold nanoparticles, Chitosan, Skin permeation enhancer, Protein, Transdermal delivery
金纳米颗粒用于增强蛋白质药物的皮肤渗透
摘要本研究旨在评价柠檬酸离子(Ci-AuNPs)和壳聚糖(CS-AuNPs)稳定的金纳米颗粒(AuNPs)对蛋白质药物异硫氰酸白蛋白-荧光素偶联物(FITC-BSA)皮肤渗透的影响。分别用Turkevich法和微波辅助法制备了Ci-AuNPs和CS-AuNPs。研究了AuNPs的粒径、表面电荷和形貌。分别采用垂直Franz扩散池、共聚焦激光扫描显微镜(CLSM)和MTT法检测AuNPs对猪皮肤的透皮性、透皮途径和安全性。AuNPs呈球形,尺寸在纳米尺度(<100 nm)。Ci-AuNPs表面带负电,CS-AuNPs表面带正电。与CS-AuNPs共同递送FITC-BSA的通透性比单独递送FITC-BSA的通透性高约3.5倍。有趣的是,Ci-AuNPs共给药没有显著改善。CLSM可视化显示,模型蛋白的传递通过经皮途径增强。此外,CS-AuNPs对正常人成纤维细胞没有明显的细胞毒性。综上所述,所开发的CS-AuNPs被认为是一种安全有效的纳米系统,可以促进蛋白质的透皮递送。关键词:金纳米颗粒,壳聚糖,促皮剂,蛋白质,透皮给药
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