Rossi Joanna, Giasson Suzanne, Khalid Mohamed Nabil, Delmas Pascal, Allen Christine, Leroux Jean-Christophe
University of Montreal, Montréal, Qué., Canada.
Eur J Pharm Biopharm. 2007 Sep;67(2):329-38. doi: 10.1016/j.ejpb.2007.03.016. Epub 2007 Mar 30.
The purpose of this study was to develop oil-in-water emulsions (100-120 nm in diameter) and to correlate the surface properties of the emulsions with blood residence time and accumulation into neoplastic tissues by passive targeting. We investigated the effect of phospholipid and sphingolipid emulsifiers, hydrogenated soybean phosphatidylcholine (HSPC) and egg sphingomyelin (ESM), in combination with polysorbate 80 (PS-80) and 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE)-PEG lipids of various PEG chain lengths and structures in prolonging circulation time and enhancing accumulation into B16 melanoma or C26 colon adenocarcinoma. The relationship between amphiphile molecular packing at the air/water interface on emulsion stability upon dilution in albumin and circulation longevity in vivo was also explored for non-PEGylated emulsions. PEGylation of the droplet surface with 10-15 mol% of DSPE-PEG 2000 or 5000 enhanced the circulation time of the emulsions, however, accumulation was only observed in the C26 tumor model. The tighter molecular packing observed with ESM/PS-80 monolayers at the air/water interface compared to HSPC/PS-80 correlated with improved emulsion stability in vitro, however, enhanced circulation time in vivo was not observed. A better understanding of the relationships between composition and performance will result in improved emulsion-based drug delivery vehicles for cancer therapy.
本研究的目的是制备水包油乳液（直径100 - 120 nm），并通过被动靶向将乳液的表面性质与血液停留时间及在肿瘤组织中的蓄积相关联。我们研究了磷脂和鞘脂乳化剂，氢化大豆卵磷脂（HSPC）和蛋黄鞘磷脂（ESM），与聚山梨酯80（PS - 80）以及不同PEG链长度和结构的1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷脂酰乙醇胺（DSPE）-PEG脂质组合，在延长循环时间以及增强在B16黑色素瘤或C26结肠腺癌中的蓄积方面的作用。对于未聚乙二醇化的乳液，还探讨了在白蛋白中稀释时空气/水界面处两亲分子堆积与乳液稳定性及体内循环寿命之间的关系。用10 - 15 mol%的DSPE - PEG 2000或5000对液滴表面进行聚乙二醇化可延长乳液的循环时间，然而，仅在C26肿瘤模型中观察到蓄积现象。与HSPC/PS - 80相比，在空气/水界面处观察到的ESM/PS - 80单分子层更紧密的分子堆积与体外更好的乳液稳定性相关，但未观察到体内循环时间的延长。更好地理解组成与性能之间的关系将有助于改进用于癌症治疗的基于乳液的药物递送载体。
