Scanning Electron-Raman Cryomicroscopy for Characterization of Nanoparticle-Albumin Drug Products.

Abstract

Nanomaterials have expanded the use of active pharmaceutical ingredients by improving efficacy, decreasing toxicity, and facilitating targeted delivery. To systematically achieve this goal, nanomaterial-containing drugs need to be manufactured with precision in attributes such as size, morphology, surface chemistry, and composition. Their physicochemical characterization is essential as their attributes govern pharmacokinetics yet can be challenging due to the nature of many nanomaterial-based formulations unless advanced sample fixation and in vitro characterization methods are utilized. Here, different cryogenic and other fixation strategies were assessed, and a novel physicochemical characterization method was developed using scanning electron Raman cryo-microscopy (SERCM). A complex nanoparticle albumin bound paclitaxel (nab-paclitaxel) formulation was chosen as a model drug. Plunge freezing (PF), high pressure freezing (HPF), freeze substitution (FS), and membrane filtration were compared for their influence on size and morphology measurements, and formulation-based variations were quantified. SERCM was introduced as a multiattribute physicochemical characterization platform, and the composition of nanoparticles was confirmed as albumin-paclitaxel complexes. By coupling image-based quantitative analysis with chemical analysis, SERCM has the potential to pave the way for the development of comprehensive tools for assessing injectable and ophthalmic nanomaterial-containing drugs in their native-like state.