Multidrug encapsulation by coaxial tri-capillary electrospray

This study describes how a coaxial tri-capillary electrospray (ES) system can synthesize monodisperse PLGA-coated particles containing multiple drugs in one step. The coaxial arrangement of three separate capillaries in an ES nozzle enables production of composite particles with tri-layered structures without the complicated steps involved in emulsion processes. Various materials can be encapsulated in separate layers of individual composite particles without regard for the hydroscopic property of drugs. At the proper spray setting, nearly 100% drug encapsulation efficiency can be achieved. By varying the feed flowrate of spray solutions, the overall particle sizes, ranging from submicrometer to micrometer, and the thickness of the layers in produced particles can also be controlled. Size and tri-layered structure of the composite particles were characterized by SEM and laser scanning confocal microscopy (LSCM). We further explored the spray technique in the production of tri-layered composite particles having a controlled multidrug-release profile, and compared the release profiles of both core-shell structured particles (produced by coaxial dual-capillary ES) and tri-layered ones (produced by coaxial tri-capillary ES). The comparison showed that composite particles with the tri-layered structure can release multiple drugs in distinct kinetic phases. We further demonstrated that the release profile of tri-layered composite particles can be effectively controlled by varying the thickness and chemical composition of their individual layers.