Wood Kurt, Szewczuk Myron R, Rousseau Dérick, Neufeld Ronald J
Department of Chemical Engineering, Queen's University, Kingston, Ontario K7L3N6, Canada.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario K7L3N6, Canada.
Oncotarget. 2018 Jan 29;9(16):12754-12768. doi: 10.18632/oncotarget.24339. eCollection 2018 Feb 27.
Pickering emulsions are colloidal dispersions stabilized by particles that either migrate to, or are formed at, the oil-water interface during emulsification. Here, we fabricated and characterized Pickering water-in-oil emulsions where molten glycerol monostearate crystallized at the surface of micron-sized water droplets and formed protective solid shells. We tested this emulsion as a reservoir delivery platform for the sustained release of low molecular weight hydrophilic molecules including sodium chloride (NaCl) and sodium citrate as model compounds, and the therapeutic oseltamivir phosphate (OP), the delivery of which was the ultimate goal of this research. The objective was to achieve long-term (30-day) release of challenging to encapsulate actives and ultimately demonstrate the sustained release of OP for 20-30 days from an injectable formulation. OP was used because of its anticancer properties targeting mammalian neuraminidase 1 (Neu1) involved in multistage tumorigenesis. All actives including OP encapsulated in Pickering emulsions displayed a near linear release profile over 30 days. It was demonstrated that the release could be modulated by the addition of a second, competing surfactant sorbitan monooleate, Span 80, to the emulsion at levels above its critical micelle concentration. OP released from the emulsions significantly reduced cell viability in the human PANC-1 pancreatic cancer cell line for up to 30 days. The findings from this study indicate a simple, potentially injectable formulation and method that is easily upscaled resulting in a stable product with the potential to fully retain small hydrophilic molecules/drugs for sustained, near linear release over days, weeks, and potentially months.
皮克林乳液是一种胶体分散体系，由在乳化过程中迁移至油水界面或在该界面形成的颗粒稳定。在此，我们制备并表征了油包水型皮克林乳液，其中熔融的单硬脂酸甘油酯在微米级水滴表面结晶并形成保护性固体壳层。我们将这种乳液作为一种储库递送平台，用于持续释放低分子量亲水性分子，包括作为模型化合物的氯化钠（NaCl）和柠檬酸钠，以及治疗性磷酸奥司他韦（OP），递送OP是本研究的最终目标。目的是实现对难以包封的活性成分的长期（30天）释放，并最终证明从注射制剂中持续释放OP达20 - 30天。使用OP是因为其针对参与多阶段肿瘤发生的哺乳动物神经氨酸酶1（Neu1）具有抗癌特性。所有包封在皮克林乳液中的活性成分，包括OP，在30天内均呈现近似线性的释放曲线。结果表明，通过在乳液中添加第二种竞争性表面活性剂单油酸山梨坦（Span 80），且添加量高于其临界胶束浓度，可以调节释放。从乳液中释放的OP在长达30天的时间内显著降低了人PANC - 1胰腺癌细胞系的细胞活力。本研究结果表明了一种简单、潜在可注射的制剂和方法，该方法易于放大规模并得到稳定的产品，有可能完全保留小的亲水性分子/药物，实现数天、数周甚至数月的持续、近似线性释放。
