This study reports physically crosslinked chitosan/αβ–glycerophosphate (CS/GP) hydrogels containing surface-modified cyclodextrin for efficient controlled drug release. Highly water-soluble β–cyclodextrin-grafted L–serine (CD–g–Ser) compounds were synthesized, and employed as an effective carrier of berberine hydrochloride (Ber) for CS/GP hydrogels. Various characterizations, including gelation time determination, scanning electron microscopy, and viscosity measurement, indicated that the introduction of CD–g–Ser led to increased crosslinking degree, improved temperature sensitivity, and shortened sol–gel phase transition time of the hydrogel. Meanwhile, the sustained release ability for Ber was achieved due to the hydrophobic association between cyclodextrin and Ber. It was observed that within 4 h, the hydrogel containing CD–g–Ser released 40 % of Ber, while the CS/GP hydrogel without CD–g–Ser released 65 % of Ber. Furthermore, in vitro bacteriostasis experiments confirmed the drug-loaded hydrogel had an excellent antibacterial effect against E. coli and S. aureus (diameter of the inhibition zone up to (16.4 and 34.7) mm, respectively), low hemolysis rate (<2 %), and high cell viability (>90 %). The findings indicate that the physical crosslinked CS hydrogel can be used as a new drug delivery system, and its excellent antibacterial effect makes it a potential wound dressing candidate.
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