A lot of demands are made on bone substitute materials. Among biocompatibility, osteoconductivity and initial mechanical stability, the release of drugs is of growing interest. The incorporation of antibiotics or drugs into biomaterials for the treatment of systemically altered bone is a step further in creating smart materials for bone grafting. Investigations on local therapy of multiple myeloma are part of the DFG Collaborative Research Centre TRR 79. Studies on the release of proteasome inhibitor bortezomib are based on materials science knowhow, pharmaceutical analytics, cell biological expertise and in vivo testing.
While mixing a suspension of fibrillar bovine collagen with pre-polymerized silicic acid, a rise of pH causes gel formation. During that step active agents (bortezomib and rifampicin) are incorporated. A monolithic and nano-porous xerogel forms by ambient drying. For tailoring drug release kinetics monoliths are powdered and sized.
In vitro release of rifampicin and bortezomib from monolithic xerogels was shown over 4 days while incubation in different solutions in static manner. The amount of released drug was influenced by the type of drug and its incorporated concentration. Xerogel granules of different fractions by size were shown to be suitable for adjusting release kinetics by utilizing different length of diffusion path. Release kinetics are characterized by an overlay of several processes. On the one hand side drug is released from monolith or granules. On the other hand side released drug is adsorbed on the surface of the sample and can be released again. Moreover by performing dynamic incubation manner, a release up to 28 days and an increase of 40% drug release in total were observed. Bortezomib loaded xerogel granules were implanted in myeloma mice. First results showed the successful bortezomib release in vivo leading to mortified myeloma cells and infiltration of tissue cells.
In conclusion, xerogels are suitable for the release of different drugs. The release is continued after the initial burst up to 28 days. Release kinetics are adjustable to relevant concentrations for in vivo studies. This kind of xerogel is a prospective supplier for local agent therapy of systemically altered bone.