Synthesizing porous nanospheres with highly efficient drug loading and sustained release through a thermal-controlled continuous stirred-tank reactor cascade

Nanospheres hold great promise for drug delivery but face challenges in achieving both high drug loading and sustained release. Here, we present a novel approach to produce porous cyclosporin A-loaded poly(lactic-<i>co</i>-glycolic acid) (PLGA) nanospheres <i>via</i> a thermal-controlled continuous stirred-tank reactor (CSTR) cascade, featuring rapid solidification of nanoemulsion droplets. This process traps more drug molecules in the nanosphere core by limiting their diffusion towards the surface and surrounding medium, resulting in a core-loaded structure. The resulting PLGA nanospheres exhibit a high cyclosporin A loading capacity and enable sustained drug release through the hydrolytic degradation of the PLGA matrix. Moreover, the total synthesis time is reduced from several hours to 40 min. The CSTR assisted manufacturing approach offers an efficient route for engineering nanospheres with high drug payloads and improved release kinetics, with broad potential for nanomedicine manufacturing.