Studies of structure-transport relationships in biodegradable polymer microspheres for drug delivery using NMR cryodiffusometry

In order to rationally design polymer vehicles for controlled drug delivery it is important to completely understand the nature and mechanisms of the structural evolution of the polymer matrix that ultimately controls drug release kinetics. NMR cryoporometry has been used previously to study drug release from polymer vehicles. However, no previous studies have employed the integrated cryoporometry and PFG NMR method known as cryodiffusometry, or explored the potential of specialized cryoporometry techniques such as scanning loops. In this work it has been shown that the true extent of the variability in structural evolution and transport properties between different batches of PLGA polymer microspheres, made in different ways, would be missed if these data were not available. Cryoporometry scanning loops have been used to determine the overall network geometry. Cryoporometry freezing curves and PFG NMR have been used to study the evolution in the pore-scale connectivity and the larger-scale inter-connectedness of the nanoporous void space following immersion of microspheres in aqueous phase. The molecular weight of the polymer used, and the presence of drug in the synthesis, have both been shown to significantly affect the trajectory of the structural evolution.