Title

Chitosan microspheres cross-linked with glyoxal for the local delivery of antibiotics

Abstract

Treatment of infection and biofilm formation in injuries and on implant devices is a clinical challenge. Local administration of antibiotics may address this challenge by maintaining high levels of antibiotics locally to prevent infection and biofilm formation while reducing potential toxicity associated with systemic dosing and induction of antibiotic resistance due to subtherapeutic antibiotic levels. This work investigated chitosan microspheres cross-linked with glyoxal for local delivery of tetracycline as a model antibiotic. Chitosan microspheres (82% DDA, MW= 250kDa) with and without 20wt% tetracycline were manufactured using water-in-oil emulsion process and then crosslinked with 3(v/v)%glyoxal. The microspheres with and without tetracycline loading were 10-50 microns in diameter, were 60-70% crosslinked based on the ninhydrin assay, and lost between 10-13% mass over 4 weeks in saline solution containing 10Opg/ml lysozyme. Tetracycline release over 4 weeks, exhibited a typical burst release profile followed by a slow release over the last two weeks at 2-6X the minimum inhibitory concentration of tetracycline (2-16μg/ml) against S. Aureus. Zone of inhibition tests confirmed inhibition ofS. Aureus in proportion to the amount of tetracycline released. The microspheres upto 200 pg/ml with and without tetracycline loading did not affect fibroblast cell growth over 5 days, did not stimulate mouse monocytes to release NO, and reduced LPS-stimulated NO release, indicating the microspheres were cytocompatible. These results suggest that glyoxal crosslinked microspheres have potential for local delivery of antibiotics for prevention of infection in wounds and on implant devices.

Publication Title

Journal of Polymer Materials

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