Gentamicin-Loaded Thermosetting Hydrogel and Moldable Composite Scaffold: Formulation Study and Biologic Evaluation

The aim was to design biodegradable drug delivery systems for gentamicin local delivery, meanwhile acting as scaffold for bone regeneration. Gentamicin-loaded thermosetting composite hydrogels were prepared combining chitosan with bovine bone substitutes (Orthoss (R) granules), beta-glycerophosphate as cross-linker, and lyophilized to obtain moldable composite scaffolds (moldable composite scaffold loaded with gentamicin [mCSG]). Diverse techniques for gentamicin loading into mCS were investigated by drug incorporation during hydrogel preparation or drug absorption on preformed mCS. Rheologic hydrogel characterization was performed. mCSGs were characterized for porosity, stability (water retention, water uptake), gentamicin release, cell seeding and proliferation, and antimicrobial effect on Escherichia coli ATCC 10356. Results show suitable gentamicin loadings were 4 mg in 1 mL thermosetting composite hydrogel starting solution, irreversible hydrogel thermosetting behavior, and cosolute effect of gentamicin on sol-gel transition. Positive results in terms of porosity (80%-86%), scaffold water uptake, and retention capability were obtained. Antibiotic in vitro release was completed in 4 h. Good cell seeding results were observed for mCSG1-5; mCSG3 and mCSG5 resulted the best as cell proliferation results. mCSG exerted bactericidal effect for 24 h, with superimposition of chitosan bacteriostatic effect in the first 4 h. The results lead to consider the drug delivery for reducing infection risk during bone open surgeries. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.