ABSTRACT
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® 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.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Bone Substitutes/chemistry , Chitosan/chemistry , Delayed-Action Preparations/chemistry , Gentamicins/administration & dosage , Hydrogels/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Cattle , Drug Delivery Systems , Escherichia coli/drug effects , Escherichia coli Infections/drug therapy , Gentamicins/pharmacology , Glycerophosphates/chemistry , Humans , Injections , Temperature , Tissue Scaffolds/chemistryABSTRACT
A gold standard for esophagus reconstruction is not still available. The present work aims to design a polymer patch combining synthetic polylactide-co-polycaprolacton and chitosan biopolymers, tailoring patch properties to esophageal tissue characteristics by a temperature-induced precipitation method, to get multilayered patches (1L, 2L, and 3L). Characterization shows stable multilayered patches (1L and 2L) by selection of copolymer type, and their M w . In vitro investigation of the functional patch properties in simulated physiologic and pathologic conditions demonstrates that the chitosan layer (patch 3L) decreases patch stability and cell adhesion, while improves cell proliferation. Patches 2L and 3L comply with physiological esophageal pressure (3-5 kPa) and elongation (20%).
