Optimized Synthesis of Poly(deoxyribose) Isobutyrate, a Viscous Biomaterial for Bone Morphogenetic Protein-2 Delivery.

Abstract

Injectable and phase-transitioning carriers from natural polysaccharides have great potential for the minimally invasive delivery of therapeutic proteins in the field of bone tissue engineering. In this study, a novel and highly viscous drug carrier was synthesized by a sequential process of deoxyribose polycondensation and esterification. The effect of synthesis parameters on the molecular weight, viscosity, and adhesion of the material was studied and correlated to temperature and time of polycondensation ( Tp and tp), time and temperature of esterification ( Te and te), and the molar ratio of the monomer ( R). The formulations were evaluated for molecular weight and distribution properties using GPC, chemical structures by FTIR and NMR spectra, and rheological properties using a rheometer. Formulations illustrated a wide range of viscosities (0.736 to 2225 Pa s), adhesion (0.896 to 58.45 N), and molecular weights (637 to 4216 Da), where viscosity was significantly reduced in the presence of low amounts of solvents (10-20%). The sustained release of BSA was observed over 42 days in vitro. The biocompatibility of poly(deoxyribose) isobutyrate (PDIB) as well as its potential as a bone morphogenetic protein delivery system was assessed in vivo using a rat ectopic bone model, where bone nodules were observed at 2 weeks. In summary, PDIB is a promising molecule with multiple applications for protein delivery, including for bone tissue engineering.