Preparation, Characterization, and In Vivo Pharmacokinetic Study of the Supercritical Fluid-Processed Liposomal Amphotericin B

Abstract

Here, we aimed to prepare and optimize liposomal amphotericin B (AmB) while using the supercritical fluid of carbon dioxide (SCF-CO2) method and investigate the characteristics and pharmacokinetics of the SCF-CO2-processed liposomal AmB. Liposomes containing phospholipids, ascorbic acid (vit C), and cholesterol were prepared by the SCF-CO2 method at an optimized pressure and temperature; conventional liposomes were also prepared using the thin film hydration method and then compared with the SCF-CO2-processed-liposomes. The optimized formulation was evaluated by in vitro hemolysis tests on rat erythrocytes and in vivo pharmacokinetics after intravenous administration to Sprague-Dawley rats and compared with a marketed AmB micellar formulation, Fungizone®, and a liposomal formulation, AmBisome®. The results of the characterization studies demonstrated that the SCF-CO2-processed-liposomes were spherical particles with an average particle size of 137 nm (after homogenization) and drug encapsulation efficiency (EE) was about 90%. After freeze-drying, mean particle size, EE, and zeta potential were not significantly changed. The stability study of the liposomes showed that liposomal AmB that was prepared by the SCF method was stable over time. In vivo pharmacokinetics revealed that the SCF-CO2-processed-liposomes were bioequivalent to AmBisome®; the hemolytic test depicted less hematotoxicity than Fungizone®. Therefore, this method could serve as a potential alternative for preparing liposomal AmB for industrial applications.

In Vivo Assessment of Thermosensitive Liposomes for the Treatment of Port Wine Stains by Antifibrinolytic Site-Specific Pharmaco-Laser Therapy

“…In conclusion, none of the newly tested formulations offered additional benefits over the prime candidate formulation composed of DPPC:DSPE-PEG (96:4; F3 ) in terms of TA:lipid ratio, E eff , and C TA . The TA E eff s are low for all formulations compared to other liposomal encapsulants ( Table S3 [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ]), which was expected as explained in Supplementary Section S3.1 . Further experiments therefore remained focused on the DPPC:DSPE-PEG (96:4) and DPPC:MPPC:DSPE-PEG (86:10:4) LUVETs.…”

“…The TA E eff s are low for all formulations compared to other liposomal encapsulants (Table S3 [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66]), which was expected as explained in Supplementary Section S3.1. Further experiments therefore remained focused on the DPPC:DSPE-PEG (96:4) and DPPC:MPPC:DSPE-PEG (86:10:4) LUVETs.…”

A Critical Review on Emerging Trends in Dry Powder Inhaler Formulation for the Treatment of Pulmonary Aspergillosis

“…This enhanced stability may be due to the static repulsion induced by the carbonic acids incorporated into the bilayer membrane. The in vivo pharmacokinetic study results in Sprague-Dawley rats, the SCF-processed liposomal AmB formulation achieved similar overall AUC (0-24h) with that of the commercial liposomal AmB formulation, AmBisome ® [97].…”

Preparation and Evaluation of Intraperitoneal Long-Acting Oxaliplatin-Loaded Multi-Vesicular Liposomal Depot for Colorectal Cancer Treatment

“…The merged image ( Figure 4 c) reveals the proper distribution of the phases (lipid and aqueous) in these particles, demonstrating an ideal formation of the vesicles. Furthermore, the uniqueness of these liposomal depots is the internal structure, which is clearly illustrated in this figure and is structurally different from that of traditional unilamellar or multilamellar liposomes [ 41 ].…”