13, 14, 15, 16, 17 These droplets are perfect templates for core-shell microspheres. Recent advances in microfluidics enable fabrication of monodisperse oil-in-water-in-oil (O/W/O) or water-in-oil-in-water (W/O/W) double emulsion droplets in a highly controlled fashion. Therefore, a facile method for fabricating monodisperse core-shell microspheres with precise control over the structure is desired. 11, 12 The resultant core-shell microspheres are polydisperse in size with little control over their characteristics moreover, the reproducibility is also poor. Conventional techniques for generating double emulsion employs high shear, reducing the encapsulation efficiency. Therefore, introduction of an additional shell layer on polymeric microspheres can significantly improve their versatility as well as functionality as delivery vehicles.Īlthough polymer-based core-shell microspheres show great promise in biomedical applications, the conventional fabrication method has limited their utilization. Active ingredients with different functions and properties can be encapsulated separately in the core and the shell to realize co-delivery. Functional groups and reagents can be attached to the surface of the shell to achieve targeted delivery. Fragile therapeutic agents protected in the cores can be completely isolated by the shell from the surrounding environment. Besides, core-shell microspheres have several additional advantages. Release kinetics can be further adjusted by varying other characteristics of the shell, such as its thickness. By choosing proper shell materials, the initial release rate can be reduced significantly and the overall release period can be prolonged. Active ingredients have to diffuse through both the core and shell before they are released. 7, 8, 9, 10 Core-shell polymer-based microspheres, with the additional shell whose properties can be tuned, offers more control over the release kinetics of the encapsulated active ingredients in the core. 7, 8, 9 This challenges the ability to release ingredients in a sustained manner. For instance, undesired initial burst release of active ingredients from polymer microspheres remains difficult to avoid. However, it remains a challenge to tailor the release profiles from these polymeric microspheres to the need of applications. 3, 4, 5, 6 Active ingredients can be trapped in the polymer matrices and released subsequently by diffusion or degradation of polymer matrices. These attributes make them attractive for encapsulation and controlled release applications. 1, 2, 3, 4 Polymer-based microspheres are convenient to fabricate, generally biocompatible, with tunable physical and chemical properties. Polymer-based systems have been extensively studied as delivery vehicles of drugs, proteins, peptides, and small interfering ribonucleic acid (siRNA). The approach of using core-shell particles as delivery vehicles creates new opportunities to customize the release kinetics of active ingredients. Microfluidic fabrication enables the generation of precisely controlled core-shell microspheres with a narrow size distribution, which enables the investigation of the relationship between the release kinetics of these microspheres and their characteristics. By contrast, adding an alginate shell to PLGA core can lead to a reduction of the initial release rate, thus extending the release period of hydrophobic actives. For example, by adding a poly(lactic-co-glycolic acid) (PLGA) shell to an alginate core, the encapsulation efficiency is enhanced and undesired leakage of hydrophilic actives is prevented. The release kinetics is significantly influenced by the material of the shell and other characteristics such as the thickness. We demonstrate that the nature of the shell material plays an important role in the properties of the core-shell delivery vehicles. The addition of a shell can significantly improve the versatility as well as functionality of these microspheres as delivery vehicles. The characteristics of core-shell microspheres can be precisely and easily tuned by manipulating the microfluidic double emulsion templates. We report a facile and robust microfluidic method to fabricate polymeric core-shell microspheres as delivery vehicles for biomedical applications.
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