Novel thermosensitive small multilamellar lipid nanoparticles with promising release characteristics made by dual centrifugation
Year: 2024
Type: article
Abstract: • Highly reproducible methodology for the preparation of thermosensitive small multilamellar lipid particles (tSMLPs) with narrow size distribution by dual centrifugation (DC) using high concentrations of DPPC/DSPC/DPPG 2 -mixtures • tSMLPs display gradually decreasing membrane distances towards the particle center and have no visible aqueous core • Cargo release from tSMLPs occurs at 42 °C and is strongly promoted by the presence of human serum albumin (HSA) or plasma, virtually no leakage at body temperature (37 °C) even in presence of HSA or plasma can be observed Thermosensitive liposomes (TSLs) have great potential for the selective delivery of cytostatic drugs to the tumor site with greatly reduced side effects. Here we report the discovery and characterization of new thermosensitive small multilamellar lipid nanoparticles (tSMLPs) with unusually high temperature selectivity. Furthermore, the temperature-dependent release of the fluorescent marker calcein from tSMLPs is enhanced by human serum albumin. tSMLPs can easily be prepared through dual centrifugation (DC) at very high lipid concentrations using dipalmitoyl and distearoyl phosphatidylcholine (DPPC, DSPC) and the phospholipid dipalmitoyl- sn -glycero-phosphatidyldiglycerol (DPPG 2 ). The new particles have a hydrodynamic diameter of about 175 nm and a narrow size distribution (PDI 0.02). tSMLPs consist of multiple lipid membranes, which become increasingly closer packed towards the particle center, and have no visible aqueous core. The particles are highly stable due to strong hydrogen bond-based membrane interactions mediated by DPPG 2 . tSMLPs can be used as carriers for water-soluble drugs (EE 25 %) entrapped within the interlamellar spaces. Based on biophysical (DSC, DLS and ITC) and morphological (cryo-EM) studies, a hypothesis is presented to explain the structural basis underlying the high temperature selectivity, as well as the unusual morphology of the new thermosensitive lipid nanoparticles.
Authors: Jonas K. Koehler, Stefanie Schmager, Johannes Schnur, Lars Gedda, Katarina Edwards, Heiko Heerklotz, Ulrich Massing
Institutions: University of Freiburg, Uppsala University, University of Toronto
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,700
Funder: Cancerfonden
Awards: G3696269072, G3746191362
OpenAlex ID: W4405766950