Preparation,Property And Control Release For β-Cyclodextrin-Liposome Synthesized By Supercritical CO₂Method

Liposomes are a kind of spherical closed vesicle with the lipid bilayer, which are based the self-assembly of amphiphilic phospholipids molecules in solution. The clearly separated hydrophilic and hydrophobic regions were their characteristics. It is worth mentioning that the water-soluble drug and oil-soluble drug can be respectively encapsulated in the inner aqueous compartment and the lipid phase, and the liposomes are widely used in the intelligent drug delivery. However, in most cases, the retention of oil-soluble drug within the lipid phase could make the bilayer unstable, thus limiting the diversity of drugs that could be associated with liposomes and the drug to lipid mass ratio. The drug-in-cyclodextrin-in-liposomes system can overcome these drawbacks.In this paper, preparation method of β-cyclodextrin-liposome was established by combination Bangham method and supercritical CO2fluid technology. Three drug-loading manners which called double drug-loading method, one-step passive drug-loading method and two-step active drug-loading method were studied in our experiments. The particle size and size distribution was characterized by the dynamic light scattering (DLS) technique. The drug content was detected by HPLC. The drug encapsulation efficiency was indirectly determinated by dialysis technique. The phase transition temperature was obtained by the DSC and the temperature-controlled release rate of drug in vitro was measured. The effects of scCO2synthesis pressure and mass ratio (β-CD:lecithin) on the size as well as drug encapsulation efficiency were studied for optimizing the preparation conditions.Experimental results showed that the aqueous solubility of VE was significantly improved in the β-CD solution. The size and drug encapsulation efficiency were controlled by adjusting scCO2pressure. By optimizing the condition of variables, the most appropriate pressure was at24MPa-25MPa and the best mass ratio (β-CD:lecithin) was0.10～0.15. For the three different drug-loading methods, the double drug-loading technique (VE-CD→VE-lipid) was chosen as the best method owing to their small size and high drug encapsulation efficiency. In vitro release results demonstrated that the drug can be have a great lot and fast release at the phase transition temperature, which was superior to the temperature above or below the phase transition temperature. Therefore, this system can be used as thermal liposomes with the release switch of phase transition temperature. It can be targeted delivery drug, causing the drugs to play a pharmacodynamics intensively at the lesion site, and ultimately improving the therapeutic effect.