Nanogels for ciprofloxacin delivery: Design, synthesis and characterization

Rosario

Congreso; Ricifa 2023; 2023

RICIFA

In the search for innovative ways to improve drug delivery, nanogels (NG) have emerged as promising nanoscale carriers. These unique materials combine gel properties with nanotechnology, and have gained attention for biomedical applications due to their ability to release bioactive substances, including drugs, in a controlled fashion. Continuous-flow devices in combination with photopolymerization methods provide a strict control over reaction conditions and allow tuning of the final properties of synthetized NG. Moreover, different stimuli, including internal or external clues, can be leveraged to trigger the dissociation or conformational changes in the NG network, facilitating the release of the payload. The aim of this work was to develop a topical antimicrobial nanocarrier based on a thermo-responsive NG, constituted by N-isopropylacrylamide (NIPA) and Bis-acrylamide (BIS), synthetized in continuous-flow reactors, loaded with ciprofloxacin (CIP), selected as antimicrobial model drug.The synthesis of the NG was performed by photoinduced polymerization in a continuous-flow device. After dialysis to remove unreacted regent, NG NIPA-BIS was obtained, and CIP was loaded through a continuous flow process. Experimental design tools were applied to rationalize the CIP loading and evaluate the performance of NIPA-BIS as carrier systems. Their interfacial properties (hydrodynamic diameter (dH), polydispersity index (PDI), and electrokinetic potential (Z)) were evaluated. The loading efficiency of CIP (EC%) was determined by UV-vis spectroscopy. In vitro release studies of CIP from NIPA-BIS-CIP were performed using bicompartmental cells, and mathematical modeling of drug release kinetics wes analyzed. The antimicrobial activity of NIPA-BIS-CIP was studied against Staphylococcus aureus and Pseudomonas aeruginosa, using the agar diffusion method. NIPA-BIS-CIP exhibited nanoscale sizes (dH = 242 ± 13 nm), narrow size distribution (PDI < 0.3) and negative Z-potential (?35 ± 2 mV). CIP was efficiently loaded (EC%: 25 ± 5 %) and NIPA-BIS-CIP achieved an effective control over CIP release, compared to the free drug, towards phosphate buffer solution at pH 7.4 (37 °C) used as receptor medium. CIP was released in a controlled manner from the NG NIPA-BIS-CIP by Fickian diffusion kinetics. Although the delivery of CIP was controlled, it allowed bactericidal effect. An in vitro bacterial growth inhibition assay showed significant CIP activity from NIPA-BIS-CIP, corresponding to 37.8 and 38% of that exhibited by a CIP solution at similar drug concentrations, against S. aureus and P. aeruginosa, respectively. NIPA-BIS-CIP showed promising behavior that could be exploited for the treatment of topical and mucosal opportunistic infections. These findings support the innovative potential of NG as effective topical delivery systems and contribute to the advancement of nanomedicine against bacterial infections.