Understanding the interaction of amorphous calcium polyphosphate with aqueous environments to optimize its use as a localized drug delivery matrix.

摘要

Amorphous calcium polyphosphate (CPP) shows potential as an implantable drug delivery matrix through a simple gelling protocol that has been shown to eliminate burst release and extend drug release time from the matrix. The nature of the interaction of CPP with aqueous environments and different drugs is not yet well understood. For this reason, CPP samples were manufactured using two different methods: the established gelation protocol, with and without drug, and mixing CPP with different volumes of aqueous solutions to better understand the effect of water exposure on the structural and drug release properties of CPP. Exposure to aqueous systems caused a reduction in the chain length of CPP that was dependant on gel time and mode of exposure. Longer gel times or increased volume of water used during exposure also caused the formation of crystalline material upon drying. In general, drug release was a function of aqueous exposure and the therapeutic agent used. Drug elution studies showed an increase in the burst release of vancomycin (VCM) from CPP gelled for extended periods. When total gel time was 10 hours or below samples that were gelled for only a short time during drug loading performed best. CPP loaded with BSA had a much slower release rate than VCM and appeared to release BSA by a different mechanism. Overall, this thesis shows that CCP drug delivery matrices can be produced with tailored properties simply by controlling processing conditions.