Application of Asymmetrical Flow Field-Flow Fractionation for Characterizing the Size and Drug Release Kinetics of Theranostic Lipid Nanovesicles

Abstract

Liposome size and in vitro release of the active substance belong to critical quality attributes of liposomal carriers. Here, we apply asymmetric flow field-flow fractionation (AF4) to characterize theranostic liposomes prepared by thin lipid film hydration/extrusion or microfluidics. The vesicles’ size was derived from multi-angle laser light scattering following fractionation (AF4) and compared to sizes derived from dynamic light scattering measurements. Additionally, we adapted a previously developed AF4 method to study zinc phthalocyanine (ZnPc) release/transfer from theranostic liposomes. To this end, theranostic liposomes were incubated with large acceptor liposomes serving as a sink (mimicking biological sinks) and were subsequently separated by AF4. During incubation, ZnPc was transferred from donor to acceptor fraction until reaching equilibrium. The process followed first-order kinetics with half-lives between 119.5–277.3 min, depending on the formulation. The release mechanism was postulated to represent a combination of Fickian diffusion and liposome relaxation. The rate constant of the transfer was proportional to the liposome size and inversely proportional to the ZnPc/POPC molar ratio. Our results confirm the usefulness of AF4 based method to study in vitro release/transfer of lipophilic payload, which may be useful to estimate the unwanted loss of drug from the liposomal carrier in vivo.

Recent microfluidic advances in submicron to nanoparticle manipulation and separation

“…3(H). 157 The external force can be hydraulic, thermal, electric, magnetic, or gravitational, and they can displace particles laterally to the side walls. 158 The migration speed of the particles is affected by the physical parameters of the particle, the applied force field and the parabolic flow profile.…”

Understanding the Degradation of Core-Shell Nanogels Using Asymmetrical Flow Field Flow Fractionation

“…This technique allows the separation of particles and molecules based on their diffusion coefficients. AF4 separation and analysis has been gaining interest in the field of nanomedicine and nanoscience [27][28][29], with increasing reports of separation nanogels and polymers by AF4 [30][31][32]. Using AF4 and measuring both the radius of gyration (R g ) (using MALS) and the hydrodynamic radius (R h ) (using DLS), differences in the internal crosslinking densities of differently sized nanogels could be determined [33].…”