Taming Visible Light-Induced\nPrecipitation Polymerization\nin Continuous Flow: Developing Thermoresponsive Nanogels for Controlled\nAntimicrobial Delivery

This\nresearch strategically combines continuous-flow\ntechnology\nand visible light-induced polymerization with the design of experiments\n(DoE) to achieve the production of thermoresponsive nanogels (NGs),\nfocusing on optimal size and polydispersity index (PDI), for further\ntherapeutic purposes. The study addressed the challenge of achieving\nstrict and predictable control over the production of NGs by designing\na precipitation polymerization methodology through a photoredox-initiating\nsystem. The methodology focused on the sustainable or environmentally\nfriendly synthesis of thermoresponsive NGs composed of <i>N</i>-isopropylacrylamide (NIPAm) and <i>N</i>,<i>N</i>′-methylenebis(acrylamide) (BIS) for drug delivery applications.\nA photoredox-initiating system utilizing a photocatalyst and sacrificial\ndonor was evaluated using a tubing flow reactor equipped with blue\nLEDs. Once the DoE was applied, NGs prepared using the selected parameters\nwere successfully produced with sizes of (177 ± 5) nm, a low\npolydispersity of 0.231 ± 0.018, spherical morphology, and thermoresponsiveness.\nThis straightforward and environmentally friendly approach offers\ninsights into the controlled synthesis of NGs with tailored properties,\nadvancing the field of nanomaterial production for various applications.\nThen, NGs were evaluated as nanocarriers of ciprofloxacin (Cip), selected\nas an antimicrobial model drug. The best conditions for drug loading\nwere determined by using continuous flow in a subsequent step after\nNG synthesis in continuous flow. The resulting PNIPAm-BIS-Cip NGs\ndemonstrated nanoscale sizes, narrow size distribution, colloidal\nstability, and acceptable drug entrapment efficiency. These NGs exhibited\ncontrolled drug release under simulated physiological conditions and\ndisplayed antibacterial activity against Pseudomonas\naeruginosa and Staphylococcus aureus, suggesting their potential as effective drug delivery systems for\nantimicrobial topical administration.