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.