Preparation and in vitro evaluation of PDEA-PAM thermosensitive hydrogels
Objective To prepare N,N-phenyldiethanolamine-polyacrylamide(PDEA-PAM)thermosensitive hydrogels loaded gentamicin sulphate and to evaluate the antibacterial properties in vitro and biocompatibility in vitro and in vivo.Methods PDEA-PAM thermosensitive hydrogels were fabricated by using N,N-diethylacrylamide(DEA)and acrylamide(AM)as the monomers,ammonium persulfate(APS)as an initiator,and biodegradable methacrylate-hyaluronic acid(HAMA)as a cross-linker.The lower critical solution temperature(LCST)was used as the evaluation index,and the one-way variable method was used to optimize the prescription.The properties of equilibrium swelling rate,deswelling rate and temperature sensitivity were characterized.Gentamicin sulphate was used as a model drug to prepare the hydrogels,and the antimicrobial properties in vitro and biocompatibility in vitro and in vivo were investigated.Results The LCST of PDEA-PAM thermosensitive hydrogels was 37℃,the equilibrium swelling rate was 58.32%,and the dissipation rate was 21.01%.Scanning electron microscopy showed the changes in the network structure of the PDEA-PAM thermosensitive hydrogels at 25,37 and 45℃,respectively,and the thermo-sensitivity analysis test similarly demonstrated the thermal characteristics of PDEA-PAM.The loading capacity of the hydrogels for gentamicin sulphate was 3.6%,and the drug-loaded hydrogels showed good antibacterial effect against both E.coli and S.aureus in vitro.Meanwhile,the cytotoxicity test,hemolysis test and organ toxicity investigation in vivo showed the hydrogels achieved antimicrobial activity in vitro along with good safety and biocompatibility.Conclusion PDEA-PAM hydrogels implement the topical administration of gentamicin sulfate with great thermal sensitivity and biocompatibility,and effectively inhibit bacterial proliferation in vitro.