Taming Visible Light-Induced Precipitation Polymerization in Continuous Flow: Developing Thermoresponsive Nanogels for Controlled Antimicrobial Delivery

Abstract

This research strategically combines continuous-flow technology and visible light-induced polymerization with the design of experiments (DoE) to achieve the production of thermoresponsive nanogels (NGs), focusing on optimal size and polydispersity index (PDI), for further therapeutic purposes. The study addressed the challenge of achieving strict and predictable control over the production of NGs by designing a precipitation polymerization methodology through a photoredox-initiating system. The methodology focused on the sustainable or environmentally friendly synthesis of thermoresponsive NGs composed of N-isopropylacrylamide (NIPAm) and N,N′-methylenebis(acrylamide) (BIS) for drug delivery applications. A photoredox-initiating system utilizing a photocatalyst and sacrificial donor was evaluated using a tubing flow reactor equipped with blue LEDs. Once the DoE was applied, NGs prepared using the selected parameters were successfully produced with sizes of (177 ± 5) nm, a low polydispersity of 0.231 ± 0.018, spherical morphology, and thermoresponsiveness. This straightforward and environmentally friendly approach offers insights into the controlled synthesis of NGs with tailored properties, advancing the field of nanomaterial production for various applications. Then, NGs were evaluated as nanocarriers of ciprofloxacin (Cip), selected as an antimicrobial model drug. The best conditions for drug loading were determined by using continuous flow in a subsequent step after NG synthesis in continuous flow. The resulting PNIPAm-BIS-Cip NGs demonstrated nanoscale sizes, narrow size distribution, colloidal stability, and acceptable drug entrapment efficiency. These NGs exhibited controlled drug release under simulated physiological conditions and displayed antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus, suggesting their potential as effective drug delivery systems for antimicrobial topical administration.