Drug release from injectable biodegradable polymeric adhesives for bone repair

Abstract

Fluid triblock ABA dimethacrylates with A blocks of 2, 4, or 8 lactic acid (LA) and B blocks of 7, 17 or 34 propylene glycol (PG) units were characterized using NMR and crosslinked polymer discs containing 2.5, 5 or 10 wt.% ketoprofen, prednisolone or chlorhexidine diacetate prepared. Disc water sorption, degradation and drug release kinetics were assessed using factorial analysis of gravimetric, acid release and UV spectroscopy studies. With shorter A blocks, conversion of oligomer ends to methacrylate moieties was raised and polymer water sorption reduced. Degradation was generally faster with shorter B and longer A blocks and due to both bulk and surface processes. Raised ketoprofen concentration enhanced polymer degradation. Early ketoprofen release was consistent with Fick's diffusion equation and declined with reduced LA block length. Prednisolone release initially followed Higuchi's equation and declined upon reducing total monomer PG concentration. With slower drug diffusion and higher polymer degradation rate linearity of ketoprofen and prednisolone release improved. Percentage chlorhexidine diacetate release decreased upon reducing A or B block length and drug concentration or particle size. Results were consistent with chlorhexidine diacetate interacting with polymer degradation products thereby slowing release of both.