Surfactant-Free Synthesis of PNIPAM-Based Smart Microgels for Drug Delivery Using a High-Gravity Rotating Packed Bed

Poly­(N-isopropylacrylamide) (PNIPAM) microgels have a number of potential biomedical applications, especially being considered as next-generation drug delivery systems. So far, nm-sized PNIPAM microgels have been commonly prepared in lab-scale experiments. In this work, nm-size controllable and monodisperse PNIPAM-based microgels were synthesized for the first time by surfactant-free precipitation polymerization using a high-gravity rotating packed bed reactor (RPB). The microgel size could be synergistically controlled by adjusting the amount of cross-linker and initiator in an RPB. Compared with the conventional stirred tank reactor, the RPB synthesis procedure could obtain a higher yield within 2 h of the reaction time. The higee level exhibited significant influence on the microgel size. Depending on the variation of the higee level, the particle size was tailored from 129 to 325 nm, and the hydrodynamic diameter was tailored from 217.7 to 805.4 nm without the usage of surfactants. In addition, different comonomers were introduced to regulate the lower critical solution temperature (LCST), achieve multiresponsiveness, and control microgel size. The in vitro DOX-loaded release demonstrated that PNIPAM-based microgels dramatically contributed to the sustained release of drugs.