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.
Highlights
The chief medicine regulatory agencies, the European Medicines Agency (EMA)and the United States Food and Drug Administration (FDA), give general definitions of liposomes, as follows: liposomes are artificially prepared vesicles composed of a bilayer and/or a concentric series of multiple bilayers separated by aqueous compartments formed by amphipathic molecules such as phospholipids that enclose a central aqueous core [1,2].Active molecules can be incorporated in the lipid bilayers and/or encapsulated in the internal aqueous core; liposomes are suitable carriers for theranostic agents that embrace various precision medicine tools for targeted therapies combining diagnosis, treatment planning, drug delivery, and response assessment [3,4]
We have recently described the characteristics of theranostic liposomes prepared by thin lipid film hydration followed by extrusion (TLH+extrusion), (F4M1), and microfluidic method (F4M2, F4M3, F4M4) [26]
A flow field-flow fractionation method was applied to study (i) the size and size distribution of theranostic nanovesicles and (ii) the transfer of a hydrophobic photosensitizer from theranostic nanoliposomes to acceptor liposomes. The latter served as an external sink, mimicking the in vivo situation when zinc phthalocyanine (ZnPc) is released from liposomal vesicles and immediately transferred to various biological sinks, mostly lipoproteins
Summary
The chief medicine regulatory agencies, the European Medicines Agency (EMA)and the United States Food and Drug Administration (FDA), give general definitions of liposomes, as follows: liposomes are artificially prepared vesicles composed of a bilayer and/or a concentric series of multiple bilayers separated by aqueous compartments formed by amphipathic molecules such as phospholipids that enclose a central aqueous core [1,2].Active molecules (e.g., therapeutic, imaging, and/or targeting agents) can be incorporated in the lipid bilayers and/or encapsulated in the internal aqueous core; liposomes are suitable carriers for theranostic agents that embrace various precision medicine tools for targeted therapies combining diagnosis, treatment planning, drug delivery, and response assessment [3,4]. Asymmetric flow field-flow fractionation (AF4) has been gaining attention as a technique, which allows thorough and detailed analysis of the size and size distribution of nanoparticle dispersions over a wide range of particle sizes irrespective of the polydispersity of the sample. It is suited for quality control of nanomaterials, including (phospho)lipid-based nanocarriers and innovative systems such as lipid nanoparticles [10,11,12]
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