Reincarnation of the Analytical Ultracentrifuge: Emerging Opportunities for Nanomedicine

Abstract

The analytical ultracentrifuge (AUC) and the modern field of analytical ultracentrifugation found its inception approximately a century ago. We highlight the scope of its major experimental opportunities as a transport-based method, contemporary and up-and-coming investigation potential for polymers, polymer−drug conjugates, polymer assemblies, as well as medical nanoparticles. Special focus lies on molar mass estimates of unimeric polymeric species, selfassemblies in solution, and (co)localization of multicomponent systems in solution alongside the material−biofluid interactions. We close with present challenges and incentives for future research.

Polymer selection impacts the pharmaceutical profile of site specifically conjugated Interferon-α2a

“…This effect was coined down to originate from increased translational frictional ratios, f/fsph, templated from the synthetic polymers on the biologic. Notwithstanding, AUC data unveiled rather accurate calculation of molecular weights of bioconjugates, since the methods of hydrodynamics inherently consider variations of translational friction properties associated to sedimentation and diffusion (the latter through translational frictional ratios, f/fsph) in molecular weight estimations [75].…”

“…Associated to sedimentation-diffusion analysis, we realized that the conjugated polymer (though of lower molecular weight than the protein) translated its much larger translational frictional properties to the protein, i.e., the biologic (Table S2). Calculated molecular weights for the protein and conjugates by sedimentation-diffusion analysis, c(s), followed the anticipations of conjugation and from MALDI-TOF MS. Again, the deceleration of the PEG conjugates compared to the protein, despite their higher molecular weights compared to the protein, is known in the scientific literature, [63,[73][74][75] also coined as a "parachute" like effect. Apparently, this effect is much reduced when using LPG conjugation as indicated here, though still being present.…”

How to Characterize the Protein Structure and Polymer Conformation in Protein‐Polymer Conjugates – a Perspective

“…The application of AUC in structural biology and for the analysis of naturally and synthetically derived macromolecules regained interest within the last years along with the rise of data processing software. [ 48,75 ] The concept of AUC is based on the sedimentation behavior of macromolecules at a given gravitational force. In general, the rate of sedimentation in the normal gravitational field of a molecule is defined but also limited by its mass.…”

PEG-Lipids: Quantitative Study of Unimers and Aggregates Thereof by the Methods of Molecular Hydrodynamics

“…The in situ observed transport of material in the cell sectors for AUC experiments allows for extraction of primary hydrodynamic data, particularly sedimentation and diffusion coefficients, associated to the materials concentration . In combination with primary data on molecular density and viscometric properties, it can decipher macromolecular and colloidal parameters, ultimately determining the molar masses of the materials in solution. ,, …”

“…The in situ observed transport of material in the cell sectors for AUC experiments allows for extraction of primary hydrodynamic data, particularly sedimentation and diffusion coefficients, associated to the materials concentration. 28 In combination with primary data on molecular density and viscometric properties, it can decipher macromolecular and colloidal parameters, ultimately determining the molar masses of the materials in solution. 10,29,30 Herein, we study the solution properties of PEG-Lipids I and II (Scheme 1) in terms of the methods of molecular hydrodynamics involving (molecular) viscometry, (molecular) densimetry, and sedimentation−diffusion analysis making use of AUC.…”