Materials Institute of Atomic and Molecular Science, Shaanxi University of Science & Technology, Xi'an, Shaanxi CN-710021, China; Université de Strasbourg, CNRS, ICS UPR 22, Strasbourg F-67000, France.
Université de Strasbourg, CNRS, ICS UPR 22, Strasbourg F-67000, France.
J Control Release. 2019 Feb 10;295:31-49. doi: 10.1016/j.jconrel.2018.12.037. Epub 2018 Dec 21.
Attractive interest on double emulsions comes from their unique morphology, making them general multifunctional carriers able to encapsulate different hydrophilic and lipophilic molecules in the same particle. Over the past century, two different types of methods were followed to prepare double emulsions for pharmaceutics applications, so-called "one-step" and "two-step" processes. The two-step approach, consisting in two different emulsifications successively performed, allows the optimal and more efficient formulations due to simplicity of principle and controllability of the process. In this review, focused on the formulation of double emulsions by two-step process, we recount the historical development of this approach, along with the state-of-the-art, including a discussion on the role of the formulation parameters, surfactants, amphiphilic polymers, interface stabilization, volume fraction, and so forth, on the final formulation stability, morphology and properties as drug delivery system. Discussion was also extended to polymeric microparticles and nanoparticles made by solvent diffusion, on the basis of double emulsions made by two-step process, along with literature review on the impact of different formulation and processing parameters. In addition, the properties of the polymers used in the microparticles matrix (molecular weight, chemical nature) potentially impacting on the ones of the microparticles formed (drug release kinetics, stability, morphology), were also discussed. Finally, the future trends in double emulsions application were addressed, emphasizing some new advances made in the emulsifications method as potentially able to open the range of applications, for example to nanoscale with spontaneous emulsification or low energy microfluidic emulsification.
双乳液的吸引力在于其独特的形态，使它们成为通用的多功能载体，能够将不同的亲水性和疏水性分子封装在同一颗粒中。在过去的一个世纪里，为了药物应用，人们采用了两种不同的方法来制备双乳液，即所谓的“一步法”和“两步法”。两步法包括连续进行两次乳化，由于原理简单且过程可控，因此可以得到最佳和更有效的配方。在这篇综述中，我们重点介绍了两步法制备双乳液的配方，回顾了这种方法的历史发展，以及最新的研究进展，包括讨论了配方参数、表面活性剂、两亲聚合物、界面稳定、体积分数等对最终配方稳定性、形态和性能的影响，以及作为药物传递系统的作用。此外，还扩展到了基于两步法制备的双乳液的溶剂扩散法制备的聚合物微球和纳米颗粒，并对不同配方和工艺参数的影响进行了文献综述。此外，还讨论了影响微球形成的聚合物的性质（分子量、化学性质），例如药物释放动力学、稳定性、形态等。最后，讨论了双乳液应用的未来趋势，强调了乳化方法的一些新进展，这些进展有可能为其应用开辟新的领域，例如纳米级的自发乳化或低能量微流控乳化。
