ABSTRACT
The properties of nanomedicines will influence how they can deliver drugs to patients reproducibly and effectively. For conventional pharmaceutical products, Chemistry, Manufacturing and Control (CMC) documents require monitoring stability and storage conditions. For nanomedicines, studying these important considerations is hindered by a lack of appropriate methods. In this paper, we show how combining radiolabelling with size exclusion chromatography, using a method called SERP (for Size Exclusion of Radioactive Polymers), can inform on the in vitro degradation of polymer nanoparticles. Using nanoparticles composed of biodegradable poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA), we show that SERP is more sensitive than dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) to detect degradation. We also demonstrate that the properties of the polymer composition and the nature of the aqueous buffer affect nanoparticle degradation. Importantly, we show that minute changes in stability that cannot be detected by DLS and NTA impact the pharmacokinetic of nanoparticles injected in vivo. We believe that SERP might prove a valuable method to document and understand the pharmaceutical quality of polymer nanoparticles.
Subject(s)
Chromatography, Gel , Nanoparticles , Polyesters , Polylactic Acid-Polyglycolic Acid Copolymer , Nanoparticles/chemistry , Chromatography, Gel/methods , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polyesters/chemistry , Animals , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Polymers/chemistry , Drug Stability , Particle SizeABSTRACT
Polyethylene glycol (PEG) is considered the gold standard to prepare long circulating nanoparticles. The hydrophilic layer that sterically protects PEGylated nanomedicines also impedes their separation from biological media. In this study, we describe an immunoprecipitation method using AntiPEG antibodies cross-linked to magnetic beads to extract three types of radiolabeled PEGylated systems: polymeric nanoparticles, liposomes, and therapeutic proteins. The potential of the method is emphasized by isolating these systems after in vivo administration and ex vivo incubation in human biological fluids. Immunoprecipitation also allows a unique perspective on the size distribution of nanoparticles in the bloodstream after intravenous and intraperitoneal administrations. Further, we highlight the potential of the approach to inform on nanomaterial-associated drug in plasma as well as help characterize the protein corona. Altogether, we believe this method answers an unmet need in nanomedicine research and will contribute a fresh perspective on the interactions of nanomedicines with biological systems.
