Production of liposomes loaded with antioxidants using a supercritical CO2 assisted process (original) (raw)
Related papers
Journal of CO2 Utilization, 2017
Liposomes are natural vesicles generally based on phosphatidylcholine (PC). The optimization of the lipid bilayer composition with the addition of little percentages of natural lipids is still at early stage due to the difficulties experienced by classical liposome formation processes, mainly, in reproducibility and encapsulation efficiency. Supercritical assisted liposome formation (SuperLip) has demonstrated that these limitations can be overcome. Therefore, in this work, this process has been tested to produce liposomes of controlled nanometric diameter and the effect of water solution flow rate on drug encapsulation efficiency was investigated. The addition of cholesterol (Chol) or phosphatidylethanolamine (PE) was also studied to gain the control on the release rate of the drug entrapped in liposomes. Theophylline was selected as the model hydrophilic drug. Using SuperLip process, PC/Chol and PC/PE liposomes were successfully produced with nanometric mean diameters down to 200 nm. Optimization of both lipid composition and SuperLip operative parameters allowed to obtain theophylline encapsulation efficiencies up to 98%. Drug release kinetics were affected by liposome composition, in particular, the addiction of Chol and PE allowed to slow down theophylline release rate. These results confirmed the possibility of producing liposomes with a complex architecture of the lipid membrane using the SuperLip process.
Chemical engineering transactions, 2017
Liposomes are spherical vesicles formed by a inner aqueous core and a double lipidic layer around it. Conventional techniques for the production of liposomes are characterized by several drawbacks, like the production of micrometric vesicles, a difficult control of the Particle Size Distribution (PSD) and low encapsulation efficiencies (EE) of hydrophilic compounds. Many supercritical semi-continuous techniques were proposed in literature. They are successful in the intent of producing liposomes of smaller diameter, but the EE of hydrophilic compounds and the reproducibility are still a challenge. For this reason, it was recently proposed a new supercritical process whose aim is to invert the steps of production of liposomes, by first creating water droplets and then to fast surround them by phospholipids. We discovered that the high diffusion coefficient of phospholipids in supercritical carbon dioxide allows a fast coverage of water droplets preserving the drug content into the li...
2021
Liposomes are spherical vesicles made of a double lipidic layer that surrounds an inner aqueous core. Several methods for the preparation of liposomes have been developed in the last decades. However, these methods present drawbacks, such as low reproducibility, batch operations, low encapsulation efficiency of hydrophilic compounds, a difficult control of liposome size distribution and high solvent residue, hindering the real industrial potential of these drug delivery systems. Supercritical fluid (SCF) technologies have been proposed to overcome several limitations of conventional processes for the production of micronized particles carriers, coprecipitates and nanocomposite polymeric structures. Recently, some techniques based on the use of supercritical carbon dioxide have been proposed also for liposome production. However, these methods have still some limitations related to the control of liposome dimension and size distribution and also show very low encapsulation efficiency...
International Journal of Pharmaceutics, 2021
Liposomes were produced by an innovative method using supercritical carbon dioxide as a dispersing agent. A quality by design strategy was used to find optimal production conditions with specific parameters (lipid concentration, dispersion volume, agitation rate, temperature and pressure) allowing the production of liposomes with predicted physicochemical characteristics (particles size and PdI). Two conditions were determined with specific production parameters. It was shown that these two conditions allowed the production of liposomes of different compositions and that most of the liposome formulations had size and dispersity in accordance with the prediction values. The condition involving the higher lipid concentration showed a higher variability in terms of size and dispersity. However, this variability remained acceptable. This innovative supercritical method allowed the production of liposomes with physicochemical characteristics similar to those obtained by the conventional thin film hydration method. This new supercritical carbon dioxide method easily scalable in GMP conditions is a one-step production method contrarily to conventional methods which generally need an additional step as extrusion to homogenize the size of liposomes.
2018
Liposomes loading -carotene were prepared utilizing supercritical carbon dioxide (SCCO2) as an alternative to organic solvent. Ultrasonication was supplied which is expected to help liposomal formation. Three -carotene samples containing different Z-isomer content (2.4%, 37%, and 87% of total -carotene) were prepared by thermal Zisomerization and encapsulated into liposomes. The size, structure and properties of the liposomes were characterized by transmission electron microscopy, UV-Visible spectrophotometry, high-performance liquid chromatography and the dynamic light scattering technique. The particle size range of liposomes was from 90 to 150 nm, and multilamellar vesicles were obtained. -carotene was incorporated to the lipid bilayer system and dispersed in water. Total amount of encapsulated -carotene increased by isomerization. Liposomes encapsulating -carotene ranged in size from 50 to 100 nm, and zeta potential described the high stability of liposomal suspension.
Supercritical assisted process for the encapsulation of olive pomace extract into liposomes
The Journal of Supercritical Fluids, 2018
Polyphenols occurring in nature are sensible to light, heat and oxygen. For this reason, it is necessary to entrap them into drug carriers, such as liposomes. In this work, the Supercritical assisted Liposome formation process (SuperLip) was used for the encapsulation of a polyphenol-rich aqueous extract from olive pomace. The effect on liposome morphology and encapsulation efficiency of different operative parameters was studied. Liposomes were produced with mean diameters smaller than 265 nm at 130 bar and down to 168 nm for 170 bar. Narrower liposome distribution curves were obtained changing the nozzle diameter for the atomization of water. Encapsulation efficiencies up to 58% were obtained, that are about six times larger than using conventional methods.
Supercritical Assisted Production of Lutein-Loaded Liposomes and Modelling of Drug Release
Processes
In this work, a lipophilic ophthalmic drug, lutein, has been entrapped in liposomes, using a supercritical assisted process. Effects of pressure, temperature, and drug to lipid ratio variation were studied on mean diameters and lutein encapsulation efficiency. Liposomes with diameters between 153 ± 38 and 267 ± 56 nm were produced, and lutein encapsulation efficiencies between 86.5 ± 0.4% and 97.8 ± 1.2% were obtained. A Scanning Electron Microscope confirmed spherical shape and mean dimensions of vesicles. The variation of temperature for the production of liposomes showed a significant impact on lutein retention time in the double lipidic layer. Lutein drug release from liposomes produced at 35 °C ended in almost 4.5 days; whereas, liposomes produced at 40 °C showed a faster lutein release in 3 days; then, vesicles obtained at 45 °C released their lutein content in only 2 days. Drug release raw data were well-fitted using Weibull model (R2 up to 99%).