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

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 psi pressure, C-discs) is superior to that of discs prepared by regular manual compaction (M-discs) for the release of VCM and EM (10 wt.%). 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 hr (55% and 60%, respectively, p < 0.05). In addition, C-discs significantly extended the VCM release (1500 hr) and EM (800 hr) as compared to M-discs (160 and 96 hr, respectively, p < 0.05). The VCM released from C-discs retained its bactericidal activity much longer (1500 hr) than that from M-discs (700 hr, p < 0.05). 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.