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单油酸甘油酯辅助的粉末疫苗油基透皮递送

Monoolein Assisted Oil-Based Transdermal Delivery of Powder Vaccine.

作者信息

Kitaoka Momoko, Oka Atsushi, Goto Masahiro

机构信息

Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, Fukuoka 819-0395, Japan.

Advanced Transdermal Drug Delivery System Center, Kyushu University, Fukuoka 819-0395, Japan.

出版信息

Pharmaceutics. 2020 Aug 27;12(9):814. doi: 10.3390/pharmaceutics12090814.

Abstract

An increasing number of protein vaccines have been researched for cancer, inflammation, and allergy therapies. Most of the protein therapeutics are administered through injection because orally-administered proteins are metabolized by the digestive system. Although transdermal administration has received increasing attention, the natural barrier formed by the skin is an obstacle. Monoolein is a common skin penetration enhancer that facilitates topical and transdermal drug delivery. Conventionally, it has been used in an aqueous vehicle, often with polyhydric alcohols. In the current study, monoolein was dissolved in an oil vehicle, isopropyl myristate, to facilitate the skin permeation of powder proteins. The skin permeabilities of the proteins were examined in-vivo and ex-vivo. Monoolein concentration-dependently enhanced the skin permeation of proteins. The protein permeability correlated with the zeta potential of the macromolecules. Dehydration of the stratum corneum (SC), lipid extraction from the SC, and disordering of ceramides caused by monoolein were demonstrated through Fourier transform infrared spectroscopic analysis and small-angle X-ray scattering analysis. An antigen model protein, ovalbumin from egg white, was delivered to immune cells in living mice, and induced antigen-specific IgG antibodies. The patch system showed the potential for transdermal vaccine delivery.

摘要

越来越多的蛋白质疫苗被用于癌症、炎症和过敏治疗的研究。大多数蛋白质疗法通过注射给药,因为口服蛋白质会被消化系统代谢。尽管透皮给药受到越来越多的关注,但皮肤形成的天然屏障是一个障碍。单油酸甘油酯是一种常见的皮肤渗透促进剂,可促进局部和透皮给药。传统上,它被用于水性载体中,通常与多元醇一起使用。在本研究中,单油酸甘油酯溶解在油性载体肉豆蔻酸异丙酯中,以促进粉末状蛋白质的皮肤渗透。在体内和体外研究了蛋白质的皮肤渗透性。单油酸甘油酯浓度依赖性地增强了蛋白质的皮肤渗透。蛋白质渗透率与大分子的zeta电位相关。通过傅里叶变换红外光谱分析和小角X射线散射分析证明了单油酸甘油酯引起的角质层(SC)脱水、SC脂质提取和神经酰胺紊乱。一种抗原模型蛋白,即蛋清中的卵清蛋白,被递送至活体小鼠的免疫细胞,并诱导产生抗原特异性IgG抗体。该贴片系统显示出透皮疫苗递送的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1139/7558954/c0dd6fd5d6eb/pharmaceutics-12-00814-g001.jpg

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