Ghanbarzadeh Saeed, Valizadeh Hadi, Zakeri-Milani Parvin
Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. ; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2013;3(1):25-9. doi: 10.5681/apb.2013.005. Epub 2013 Feb 7.
The major limitation in the widespread use of liposome drug delivery system is its instability. Lyophilization is a promising approach to ensure the long-term stability of liposomes. The aim of this study was to prepare sirolimus-loaded liposomes, study their stability and investigate the effect of lyophilization either in the presence or in the absence of lyoprotectant on liposome properties.
Two types of multi-lamellar liposomes, conventional and fusogenic, containing sirolimus were prepared by modified thin film hydration method with different ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol and dioleoylphosphoethanolamine (DOPE), and were lyophilized with or without dextrose as lyoprotectant. Chemical stability investigation was performed at 4°C and 25°C until 6 months using a validated HPLC method. Physical stability was studied with determination of particle size (PS) and encapsulation efficiency (EE %) of formulations through 6 months.
Chemical stability test at 4°C and 25°C until 6 months showed that drug content of liposomes decreased 8.4% and 20.2% respectively. Initial mean EE % and PS were 72.8 % and 582 nm respectively. After 6 months mean EE % for suspended form, lyophilized without lyoprotectant and lyophilized with lyoprotectant were 54.8 %, 62.3% and 67.1 % at 4°C and 48.2%, 60.4 % and 66.8 % at 25°C respectively. Corresponding data for mean PS were 8229 nm, 2397 nm and 688nm at 4°C and 9362 nm, 1944 nm and 737 nm at 25°C respectively.
It is concluded that lyophilization with and without dextrose could increase shelf life of liposome and dextrose has lyoprotectant effect that stabilized liposomes in the lyophilization process.
脂质体药物递送系统广泛应用的主要限制在于其不稳定性。冻干是确保脂质体长期稳定性的一种有前景的方法。本研究的目的是制备载有西罗莫司的脂质体，研究其稳定性，并研究在有或没有冻干保护剂的情况下冻干对脂质体性质的影响。
通过改良薄膜水化法，以不同比例的二棕榈酰磷脂酰胆碱（DPPC）、胆固醇和二油酰磷脂酰乙醇胺（DOPE）制备了两种含西罗莫司的多层脂质体，即常规脂质体和融合脂质体，并在有或没有葡萄糖作为冻干保护剂的情况下进行冻干。使用经过验证的高效液相色谱法在4°C和25°C下进行化学稳定性研究，直至6个月。通过测定制剂6个月的粒径（PS）和包封率（EE%）来研究物理稳定性。
在4°C和25°C下进行6个月的化学稳定性测试表明，脂质体的药物含量分别下降了8.4%和20.2%。初始平均EE%和PS分别为72.8%和582nm。6个月后，在4°C下，悬浮形式、无冻干保护剂冻干和有冻干保护剂冻干的平均EE%分别为54.8%、62.3%和67.1%，在25°C下分别为48.2%、60.4%和66.8%。4°C下平均PS的相应数据分别为8229nm、2397nm和688nm，25°C下分别为9362nm、1944nm和737nm。
得出结论，有或没有葡萄糖的冻干均可延长脂质体的保质期，且葡萄糖具有冻干保护作用，可在冻干过程中稳定脂质体。
