Impacts of compacting methods on the delivery of erythromycin and vancomycin from calcium polyphosphate hydrogel matrices.

Abstract

Designing hydrogels for controlled drug delivery remains a big challenge. We developed a calcium polyphosphate hydrogel (CPP) as matrix for delivery of vancomycin (VCM) and erythromycin (EM) by unique ionic binding and physical wrapping. In this continuing study, we investigated if gel discs prepared by mechanical compaction (at 3000\u2009psi pressure, C-discs) is superior to that of discs prepared by regular manual compaction (M-discs) for the release of VCM and EM (10\xa0wt.%). Data demonstrated a significant reduction of burst release of VCM and EM in C-discs (1.8% and 5%, respectively) as compared to that from M-discs within 72\u2009hr (55% and 60%, respectively, p\xa0<\u20090.05). In addition, C-discs significantly extended the VCM release (1500\u2009hr) and EM (800\u2009hr) as compared to M-discs (160 and 96\u2009hr, respectively, p\xa0<\u20090.05). The VCM released from C-discs retained its bactericidal activity much longer (1500\u2009hr) than that from M-discs (700\u2009hr, p\xa0<\u20090.05). Raman Spectroscopy indicated an ionic bond of both VCM and EM with fully hydrated polyphosphate chains of CPP hydrogel matrix for both M-discs and C-discs. Micro CT showed that C-discs had much denser microstructures and less number/depth of microcracks as a result of high pressure. We propose that CPP hydrogel represents an excellent tool for the controllable and sustained delivery of VCM and EM. Extensive experiments are currently underway to evaluate the potential impacts of the modification of compaction techniques, other antibiotics, gel concentrations on the drug release, degradation behavior and infection control both in vitro and in vivo.