Research On Preparation Of Modified Phospholipid Liposomes By Supercritical Solution Rapid Expansion (RESS)

Liposomes have a phospholipid bilayer structure similar to biological cells.They are also called“artificial biofilms”and“artificial cells”due to their good biocompatibility.This compatibility enables targeted or efficient delivery of drugs.Therefore,liposomes have received widespread attention in the fields of pharmaceutical preparations and cosmetics in recent years.The ideal liposomes should have good histocompatibility,low toxicity,suitable drug encapsulation ability and release ability,etc.Traditional liposome preparation methods will inevitably use organic solvents.Recently,a green preparation process named supercritical carbon dioxide rapid expansion(RESS)process has been developed to prepare liposomes.However,the solubility of traditional phospholipids in SC-CO₂ is relatively low,which limits the application of RESS on liposomes preparation.In this study,a modified carbon dioxide-philic phospholipid and vitamin E acetate(VEA)was used as membrane material and model drug to prepare liposomes using RESS.The effects of process conditions on n the properties of the prepared liposomes were discussed in detail.In addition,to further improve the performance of liposomes,the VEA-paeonol co-loaded liposomes were also prepared and compared with the VEA liposomes.This study focuses on the following four aspects:(1)In order to provide basic data for the process of preparing modified phospholipid liposomes by supercritical technology,the static cloud point method was used to determine the VEA in SC-CO₂ with ethanol(0.5,1.0 and 2.0 mol%)as a co-solvent at the temperature of313.15 K,318.15 K,323.15 K and 328.15 K,and the pressure of 8-15 MPa.The experimental results show that the solubility of VEA in SC-CO₂ can be significantly increased by adding ethanol as a co-solvent.Furthermore,the solubility of VEA increases with the increasing pressure and decreasing temperature at a constant ethanol concentration.In addition,six typical density-based semi-empirical equations named Christil-G,KJ,Bartle,MST-S,Reddy,and Pérez,are used to correlate the experimental data.The AARD values of these models range from 2.43 to 6.86.%,indicating that these models can well predict the solubility data of VEA in SC-CO₂.(2)The solubility of paeonol in SC-CO₂ at the temperature of 313.15 K,318.15 K,323.15K,328.15 K,333.15 K,and the pressure of 8-15 MPa was also measured by the cloud point method.The experimental results show that the enhancing pressure and temperature gradually increases the solubility of paeonol in SC-CO₂ during the experimental range.In addition,four density-based semi-empirical models are used to correlate and predict the experimental results.The AARD(%)values of the Bartle,MST,Ch and Madras,and Gordillo models are 9.05%,9.37%,8.75%,and 8.49%,respectively,indicating the models can well correlate the experimental data.(3)The modified SC-CO₂-philic phospholipid was used as membrane materials to prepare VEA loaded liposomes via the RESS process.Under the predicted optimal preparation conditions,the liposomes with a spherical or ellipsoidal vesicle-like structure were successfully prepared.The average particle size and the encapsulation efficiency were 247.4 nm and92.86±0.98%,PDI and Zeta potential was 0.295±0.012 and-42.55±0.64 mV respectively.In addition,the good photothermal stability and the sustained release can be observed during the performance testing of the prepared liposomes.es are consistent with the characteristics of rapid release followed by slow release.(4)The modified SC-CO₂-philic phospholipid was used as membrane materials to prepare VEA-Paeonol co-loaded liposome by the RESS process at the pressure of 25 MPa and the temperature of 55?.The prepared co-loaded liposomes have a spherical vesicle-like structure.The average particle size,PDI and Zeta potential of the co-loaded liposomes was 271±7.8 nm,0.264±0.022,and-44.7±0.98 mV,respectively.The storage stability and the scavenging ability of DPPH free radicals of the VEA-paeonol co-loaded liposomes were better than those of the VEA liposomes.