Carboxylated phytosterol derivative-introduced liposomes for skin environment-responsive transdermal drug delivery system
Carboxylated phytosterol derivative-introduced liposomes for skin environment-responsive transdermal drug delivery system
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DOI：
10.1080/08982104.2017.1369995
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发表时间：
2018-10
影响因子：
4.4
通讯作者：
N. Yamazaki;S. Yamakawa;Takumi Sugimoto;Yuta Yoshizaki;Ryoma Teranishi;Takaaki Hayashi;Aki Kotaka;C. Shinde;Takayuki Kumei;Yasushi Sumida;Toru Shimizu;Y. Ohashi;E. Yuba;Atsushi Harada;K. Kono
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文献类型：
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作者：
N. Yamazaki;S. Yamakawa;Takumi Sugimoto;Yuta Yoshizaki;Ryoma Teranishi;Takaaki Hayashi;Aki Kotaka;C. Shinde;Takayuki Kumei;Yasushi Sumida;Toru Shimizu;Y. Ohashi;E. Yuba;Atsushi Harada;K. Kono
摘要经皮给药系统是治疗皮肤相关疾病和化妆品开发的关键技术。将活性成分递送到适当的部位或靶细胞可以大大提高医疗和美容剂的功效。对于这项研究，脂质体为基础的透皮给药系统的开发使用pH响应的植物甾醇衍生物作为脂质体成分。以植物甾醇的羟基为原料，通过酯化反应合成了琥珀酰化植物甾醇（Suc-PS）和2-羧基-环己烷-1-羧基化植物甾醇（CHex-PS）。通过在碱性pH下的负zeta电位和zeta电位随pH降低的变化证实了植物甾醇衍生物对1，2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）脂质体的修饰。含Suc-PS和CHex-PS-含有脂质体的脂质体在皮肤基底膜处的黑素细胞的细胞内酸性区室处显示出内容物释放。含有植物甾醇衍生物的脂质体被鼠黑素瘤衍生的B16-F10细胞摄取。这些脂质体将其内容物递送到B16-F10细胞的内体和胞质溶胶中。此外，含有植物甾醇衍生物的脂质体穿透3D皮肤模型并到达基底膜。结果表明，含有DMPC的pH响应性植物甾醇衍生物脂质体有希望用于经皮向黑素细胞递送医疗或化妆品试剂。
Abstract Transdermal drug delivery systems are a key technology for skin-related diseases and for cosmetics development. The delivery of active ingredients to an appropriate site or target cells can greatly improve the efficacy of medical and cosmetic agents. For this study, liposome-based transdermal delivery systems were developed using pH-responsive phytosterol derivatives as liposome components. Succinylated phytosterol (Suc-PS) and 2-carboxy-cyclohexane-1-carboxylated phytosterol (CHex-PS) were synthesized by esterification of hydroxy groups of phytosterol. Modification of phytosterol derivatives on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes was confirmed by negatively zeta potentials at alkaline pH and the change of zeta potentials with decreasing pH. In response to acidic pH and temperatures higher than body temperature, Suc-PS-containing and CHex-PS-containing liposomes exhibited content release at intracellular acidic compartments of the melanocytes at the basement membrane of the skin. Phytosterol-derivative-containing liposomes were taken up by murine melanoma-derived B16-F10 cells. These liposomes delivered their contents into endosomes and cytosol of B16-F10 cells. Furthermore, phytosterol-derivative-containing liposomes penetrated the 3 D skin models and reached the basement membrane. Results show that pH-responsive phytosterol-derivative-containing DMPC liposomes are promising for use in transdermal medical or cosmetic agent delivery to melanocytes.