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

Liposomes,which were used to carry the targeted drugs through the epidermis,have attracted much attention in pharmaceutical and cosmetic industries.Traditional methods of preparing liposomes would use organic solvents,which were harmful to the environment and products.Supercritical carbon dioxide?SC-CO₂?is a recognized green solvent,and the process of preparing liposomes by supercritical rapid expansion method is more environmentally friendly.In this paper,the liposome encapsulation process of water-insoluble drug vitamin E acetate?VEA?and water-soluble drug catechin was studied by supercritical rapid expansion method?RESS?,and the effect of process conditions on the properties of liposome was discussed.This paper included the following three aspects:?1?In order to provide basic data for liposomes preparation by supercritical technology,static cloud point method was used to measure the solubility of VEA in SC-CO₂ at temperatures of 308.15 K,313.15 K,318.15 K,323.15 K,328.15 K and pressures range from 8 to 15 MPa.The experimental results showed that,with the increase of pressure and the decrease of temperature,the solubility of VEA in SC-CO₂would gradually increase.In addition,four classical density-based semi-empirical equations were used to correlate experimental data.The results calculated by Chrastil,Kumar-Johnston?K-J?,Bartle and mendez-santiago-Teja?MST?methods were all good,and the AARD values were 6.62%,6.83%,6.80%and 7.19%,respectively.?2?The liposome preparation for water-insoluble drugs by RESS process was studied by using VEA as the model drug.Firstly,the effects of temperature,pressure and the amount of ethanol on the EE,PDI and Zeta potential of VEA liposomes were investigated by single-factor experiment.The range of optimum conditions for preparation of VEA liposomes were determined.On this basis,the interaction between the above three parameters and their influence on the EE of VEA liposomes were studied by the response surface optimization experiment.And the experimental model and correlation equation were obtained.The model gave the best conditions for liposome preparation:the temperature of 59.55?,pressure 23.45 MPa and 0.36 wt%ethanol.Under the best preparation conditions,the EE of VEA liposome was up to98.63±0.42%and the average particle size was about 233.4 nm,with spherical or ellipsoidal vesicular structures.During the functional test,after 7 weeks of storage,the VEA liposomes showed good photo-thermal stability and no precipitation.In addition,the in vitro release characteristics were consistent with the characteristics of rapid release first and then slow release.?3?The water-soluble nutrient liposomes were prepared by the above-mentioned RESS process with catechin as the model drug.Similarly,the effects of temperature,pressure,and p/c ratio on the EE,PDI,and Zeta potential of catechin liposomes were investigated by single-factor experiments.The range of optimum conditions for preparation of catechin liposomes were determined.Then,Box-Behnken experiment was conducted to investigate the interaction between the three factors and their effects on the EE of liposomes.Through the model and the response surface analysis,we found that the best preparation conditions were temperature of 56.34?,pressure of19.99 MPa,and p/c ratio of 5.99:1,the ideal EE of catechin liposome was 64.52%.After tested experimentally,the EE of liposomes was 61.36±1.08%.The average particle size of catechin liposomes was about 200 nm with spherical or ellipsoidal vesicular structure.It was found that the DPPH scavenging ability of catechin liposomes was weaker than that of catechin,indicating that the phospholipid material could effectively protect catechin from oxidation.In vitro release test showed that catechin liposomes showed a slow release behavior,which could improve the drug's utilization.