Nuclear Magnetic Resonance Spectroscopy: A Multifaceted Toolbox to Probe Structure, Dynamics, Interactions, and Real-Time In Situ Release Kinetics in Peptide-Liposome Formulations.

Liposomal formulations represent attractive biocompatible and tunable drug delivery systems for peptide drugs. Among the tools to analyze their physicochemical properties, nuclear magnetic resonance (NMR) spectroscopy, despite being an obligatory technique to characterize molecular structure and dynamics in chemistry as well as in structural biology, yet appears to be rather sparsely used to study drug-liposome formulations. In this work, we exploited several facets of liquid-state NMR spectroscopy to characterize liposomal delivery systems for the apelin-derived K14P peptide and K14P modified by Nα-fatty acylation. Various liposome compositions and preparation modes were analyzed. Using NMR, in combination with cryo-electron microscopy and dynamic light scattering, we determined structural, dynamic, and self-association properties of these peptides in solution and probed their interactions with liposomes. Using 31P and 1H NMR, we characterized membrane fluidity and thermotropic phase transitions in empty and loaded liposomes. Based on diffusion and 1H NMR experiments, we localized and quantified peptides with respect to the interior/exterior of liposomes and changes over time and upon thermal treatments. Finally, we assessed the release kinetics of several solutes and compared various formulations. Taken together, this work shows that NMR has the potential to assist the design of peptide/liposome systems and more generally drug delivery systems.

Particle Deposition Kinetics of Colloidal Suspensions in Microchannels at High Ionic Strength.

Despite its considerable practical importance, the deposition of real Brownian particles transported in a channel by a liquid, at small Reynolds numbers, has never been described at a comprehensive level. Here, by coupling microfluidic experiments, theory, and numerics, we succeed in unravelling the problem for the case of straight channels at high salinity. We discover a broad regime of deposition (the van der Waals regime) in which particle-wall van der Waals interactions govern the deposition mechanism. We determine the range of existence of the regime, for which we calculate the concentration profiles, retention profiles, and deposition kinetics analytically. The retention profiles decay as the inverse of the square root of the distance from the entry, and the deposition kinetics are given by the expression [Formula: see text], where S is a dimensionless deposition function, A is the Hamaker constant, and ξL is a dimensionless parameter characterizing fluid flow properties. These findings are well supported by numerics. Experimentally, we find that the retention profiles behave as x-0.5±0.1 (where x is the distance from the channel entry) over three decades in scale, as predicted theoretically. By varying the flow conditions (speed, geometry, surface properties, and concentration) so as to cover four decades in ξL and taking the Hamaker constant as a free parameter, we accurately confirm the theoretical expression for the deposition kinetics. Operating in the van der Waals regime enables control of the deposition rates via surface chemistry. From a surface science perspective, working in the van der Waals regime enables us to measure the Hamaker constants of thousands of particles in a few minutes, a task that would take a much longer time to perform with standard AFM.