Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, C/ Prof. García González, 2, 41012, Seville, Spain.
Department of Physical Chemistry, Faculty of Chemistry, Universidad de Sevilla, C/ Prof. García González, 1, 41012, Seville, Spain.
AAPS PharmSciTech. 2019 Aug 20;20(7):294. doi: 10.1208/s12249-019-1492-y.
Liposomes with their capacity to anchor gold nanoparticles (AuNPs) onto their surface are used in the treatment of several pathologies such as cancer. The objective of this work was the optimization of the vesicle composition by using cationic agents in order to reinforce the anchoring process of AuNPs, and for the study of the influence of local temperature and vesicle size on drug release. A Plackett-Burman design was conducted to determine the optimal composition for the anchoring of AuNPs. A comprehensive study of the influence of lipid bilayer composition on the surface charge, size, and polydispersity index (PdI) of liposomes was carried out. Afterwards, in vitro release studies by dialysis were performed and several release parameters were evaluated as a function of temperature. Cholesterol was fixed as the rigid agent and Didodecyldimethylammonium bromide (DDAB) was selected as the cationic lipid into the liposome bilayer. Photomicrographs revealed that DDAB facilitated the anchoring of AuNPs onto the liposomal surface. The anchoring of AuNPs also enhanced the amount and rate of calcein released, especially in extruded samples, at several incubating temperatures. In addition, it was observed that both the anchoring of AuNPs and the calcein release were improved by increasing the surface of the vesicles. The contributions of liposome composition (DDAB inclusion, incubation temperature, anchoring of AuNPs) and size and surface availability of the vesicles on calcein release could be used to design improved lipid nanostructures for the controlled release of anticancer drugs.
脂质体能够将金纳米粒子（AuNPs）锚定在其表面，用于治疗多种疾病，如癌症。本工作的目的是通过使用阳离子试剂优化囊泡的组成，以增强 AuNPs 的锚定过程，并研究局部温度和囊泡大小对药物释放的影响。采用 Plackett-Burman 设计来确定用于 AuNPs 锚定的最佳组成。综合研究了脂质双层组成对脂质体表面电荷、粒径和多分散指数（PdI）的影响。之后，通过透析进行了体外释放研究，并评估了几个释放参数作为温度的函数。胆固醇被固定为刚性试剂，双十二烷基二甲基溴化铵（DDAB）被选为阳离子脂质进入脂质体双层。显微镜照片显示 DDAB 有助于 AuNPs 锚定在脂质体表面。AuNPs 的锚定还增强了钙黄绿素的释放量和释放速率，尤其是在几种孵育温度下的挤出样品中。此外，观察到 AuNPs 的锚定和钙黄绿素的释放都通过增加囊泡的表面积得到改善。脂质体组成（DDAB 包含、孵育温度、AuNPs 的锚定）以及囊泡的大小和表面可用性对钙黄绿素释放的贡献可用于设计用于控制释放抗癌药物的改良脂质纳米结构。
