Microfluidic preparation of PLGA microspheres as cell carriers with sustainable Rapa release

The current study, inspired by the immunosuppressive property of rapamycin (Rapa) and the benefit of microspheres both as drug delivery system and cell carriers, was designed to develop an efficient Rapa delivery system with tunable controllability to facilitate its local administration. A capillary-based two-phase microfluidic device was designed to prepare monodisperse poly(lactide-co-glycolide) (PLGA) microspheres to load Rapa (PLGA-Rapa-M). The physical and chemical properties of PLGA-Rapa-M were characterized, and the Rapa loading capacity and release profile were explored. Chondrocytes were chosen as a cell model to evaluate the adhesion and proliferation on these microspheres. Controllability over the microsphere properties was illustrated. The PLGA-Rapa-M is averagely 63.91 μm in size with a narrow size distribution and a CV of 2.44%. The encapsulation efficiency of Rapa within microspheres via the current microfluidics was around 98%, and Rapa loading could be easily varied with a maximum value of ∼20%. The PLGA-Rapa-M has a sustained Rapa release duration of ∼3 months. These microspheres could not only successfully be used for Rapa sustained release but also as cell carriers for cell therapy since they can support the attachment/proliferation of chondrocytes. Hence, improved therapeutic index could be expected by using the current developed Rapa-release system.