Engineering drug delivery vehicles with multiphase microfluidics

Abstract

Successful therapies often require the use of drugs, which should be delivered to the target and be released for a certain period of time. To achieve targeted release with a suitable drug release profile, the drug delivery vehicles that first encapsulate and subsequently release the drugs need to be tailored. Conventional drug delivery vehicles, such as polymer microspheres, enable the tuning of the drug release profiles by varying their size, size distribution, as well as the degradation rates of the microspheres. However, more complex release profiles, such as zeroth order release, cannot be easily achieved with polymer microspheres. Moreover, important current approaches to prepare these polymer microspheres are often emulsion-based; they typically involve the use of organic solvents, which may lead to degradation of the drugs involved. Furthermore, certain therapies require the use of a cocktail of multiple drugs, which can include both hydrophilic and hydrophobic drugs. Co-encapsulation and sequential release of hydrophilic and hydrophobic drugs are challenging to achieve with existing drug delivery vehicles. Therefore, novel approaches to fabricate delivery vehicles for encapsulating both hydrophilic and hydrophobic drugs, with complicated drug release kinetics, without the use of organic solvents, are desired. In our work, we propose the use of multiphase microfluidics to prepare drug delivery vehicles with complex structures, such as core-shell capsules, multicompartment microspheres and nonspherical particles; by tailoring the spatial distribution of drugs, unconventional drug release profiles can be achieved. To avoid the use of harmful organic solvents, we introduce the use of aqueous two-phase systems in microfluidics to generate the emulsion templates for making these novel delivery vehicles. By manipulating the interfacial characteristics of the emulsion templates, complex structures with hydrophilic and hydrophobic compartments can be prepared for separate encapsulation and sequential release of both hydrophilic and hydrophobic drugs. We will discuss the fundamental problems that need to be addressed to generate these drug delivery vehicles and highlight their potential by demonstrating their release characteristics.