One-Step Precise Characterization of Drug Delivery Systems by PULCON Magnetic Resonance Spectroscopy

Polymers are extensively used for the realization of drug delivery systems across multiple scales, from nanomedicines to microparticles and macroscopic implantable devices, for their favorable biodegradation profiles and tunable physicochemical features. The accurate quantification of the polymer content is key to finely controlling drug loading and release and ensuring reproducibility, yet it continues to be a major challenge in the design and development of delivery systems. In this study, we introduce a novel protocol based on the PULCON technique to quantify, with a routine NMR spectroscopy analysis, the precise concentration of polymers in various delivery systems. Specifically, the PULCON protocol is applied to characterize the physicochemical and pharmaceutical properties of nanoparticles, microparticles, and implantable devices realized by combining three extensively used polymers, namely, poly(lactic-co-glycolic acid) (PLGA), poly(vinyl alcohol) (PVA), and poly(ethylene glycol) (PEG). Without using internal calibration procedures, in a single step, the PULCON protocol precisely quantifies the concentration of each polymer and the drug content. This approach can be readily implemented on standard NMR spectrometers, enabling accurate characterization of drug delivery systems and facilitating their effective development.