PREPARATION AND PHYSICOCHEMICAL CHARACTERIZATION OF THERMOSENSITIVE LIPOSOMES FOR ANTIBODY DELIVERY

Liposomes are sophisticated nanoparticle-based drug delivery systems. In special, thermosensitive liposomes (TSL) show distinct characteristics due to unique properties determined by the phase transition temperature (Tm) of their lipid components, being particularly advantageous for sustaining drug concentrations, tissue targeting precision and dosage adjustment under thermal exposure. In this study, we prepared and characterized TSL looking forward to their application as antibodies loading nanocarriers. Liposomes production conditions were optimized by selecting the lipid composition, extrusion process, phase transition temperature and colloidal stability parameters. Liposomes were prepared by extrusion (100 and 200 nm membranes pore) by using dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC) or distearoylphosphatidylcholine (DSPC) as unique systems or associated with distearoylphosphoethanolamine-polyethylene glycol (DSPE-PEG 2000) at 95:5 % ratio (lipid:PEG) and 5 mM as final concentration. Liposomes were characterized by Differential Scanning Calorimetry (DSC), Dynamic Light Scattering (DLS) and Zeta potential for determining the lipids bilayers phase transition temperature (Tm) and colloidal stability parameters such as hydrodynamic diameter (Dh), polydispersion index (PDI) and the potential between liposomes surface and surrounding medium (ζ). Thermal analysis revealed an increase in Tm values: 24.1; 41.6 and 54.4 °C for DMPC, DPPC and DSPC, respectively, showing the influence of acyl chain length on lipids gel-liquid phases transition. However, the incorporation of DSPE-PEG induced slight shifts on Tm values only for DPPC (42.8 °C) and DSPC (55.1 °C). Regarding colloidal parameters, Dh values were 141.2 ± 0.6 (DMPC), 124.4 ± 0.6 (DPPC) and 148.5 ± 1.5 (DSPC) nm, with PDI from 0.11 to 0.15, indicating the system’s homogeneity and the reduced dimensions upon extrusion process and DSPE-PEG incorporation. Similar findings were obtained from zeta potential analysis, where the DSPE-PEG incorporation enhanced the liposomes colloidal stability (ζ from -21.5 to – 25.2 mV). Therefore, different TSL liposomes compositions were optimized considering their phase transition temperatures modulation, homogeneous diameters distribution and adequate colloidal stability, provided by both extrusion process and DSPE-PEG incorporation. All those features highlighted essential properties for obtaining TSL with different lipid associations and their potential as antibodies nanocarriers for future skin delivery applications.