Alginate-Based Nanocomposite Incorporating Chitosan Nanoparticles: A Dual-Drug Delivery System for Infection Control and Wound Regeneration Publisher



Mousavi SJ¹ ; Heydari P^{2, 3} ; Javaherchi P² ; Kharazi AZ^{1, 2} ; Zarrabi A^{4, 5} Show Affiliations
Source: Journal of Drug Delivery Science and Technology Published:2025

Abstract

In this study, a hydrogel-based nanocomposite was fabricated as a novel wound dressing and drug delivery system. Initially, insulin-loaded chitosan nanoparticles (CSNP-INS) were produced using the ionic gelation technique. Subsequently, the CSNP-INS were introduced into ciprofloxacin-loaded sodium alginate (SA-Cip) hydrogel at two different concentrations (0.5 % and 1 % w/v), followed by crosslinking with CaCl2 after freeze-drying to enhance its physical and biological properties. The CSNP-INS nanoparticles had an average size of 173.6 ± 1.76 nm and effectively encapsulated 70 % of the INS. Physicochemical characterization revealed that SA-Cip/1%CSNP-INS has significant swelling (2996 ± 31.55 %) and high hydrophilicity (16.94 ± 0.99°), along with slow degradation due to the electrostatic interaction between CSNP and SA hydrogel (80 % weight loss after 14 days). Moreover, the mechanical properties were enhanced due to the higher concentration of CSNP (83 ± 1.9 kPa), with a Young's modulus of 83 ± 1.9 kPa. The release profile of INS after incorporation of CSNP-INS into the hydrogel was slower and more sustained. On the other hand, Cip showed a burst release (100 % within 6 h). In vitro assays of the fabricated hydrogels on fibroblastic cells demonstrated high cell viability, enhanced cell migration, and complete in-vitro wound closure (100 % within 24 h). Further analysis of the inflammatory response of hydrogels revealed a significant impact on modulating inflammation markers including a decrease in TNF-α and an increase in TGF-β. Cip and INS facilitate different wound-healing stages, ensuring efficient and accelerated wound healing. This study underscores the potential of the developed hydrogel as groundbreaking wound dressing, offering enhanced wound healing capabilities through an innovative mechanism of controlled and sustained drug release. © 2025 Elsevier B.V.