School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, L3 3AF, Liverpool, UK.
Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston, PR1 2HE, UK.
AAPS PharmSciTech. 2018 Jan;19(1):262-274. doi: 10.1208/s12249-017-0793-2. Epub 2017 Jul 11.
Formulation effects on the entrapment of beclometasone dipropionate (BDP) in liposomes generated by hydration of proliposomes were studied, using the high-density dispersion medium deuterium oxide in comparison to deionized water (DW). Proliposomes incorporating BDP (2 mol% of the lipid phase consisting of soya phosphatidylcholine (SPC) and cholesterol; 1:1) were manufactured, using lactose monohydrate (LMH), sorbitol or D-mannitol as carbohydrate carriers (1:5 w/w lipid to carrier). Following hydration of proliposomes, separation of BDP-entrapped liposomes from the unentrapped (free) BDP at an optimized centrifugation duration of 90 min and a centrifugation force of 15,500g were identified. The dispersion medium was found to have a major influence on separation of BDP-entrapped liposomes from the unentrapped drug. Entrapment efficiency values were higher than 95% as estimated when DW was used. By contrast, the entrapment efficiency was 19.69 ± 5.88, 28.78 ± 4.69 and 34.84 ± 3.62% upon using DO as a dispersion medium (for LMH-, sorbitol- and D-mannitol-based proliposomes, respectively). The similarity in size of liposomes and BDP crystals was found to be responsible for co-sedimentation of liposomes and free BDP crystals upon centrifugation in DW, giving rise to the falsely high entrapment values estimated. This was remedied by the use of DO as confirmed by light microscopy, nuclear magnetic resonance (HNMR), X-ray diffraction (XRD) and entrapment studies. This study showed that carrier type has a significant influence on the entrapment of BDP in liposomes generated from proliposomes, and using DO is essential for accurate determination of steroid entrapment in the vesicles.
研究了通过前体脂质体水合生成的脂质体来包封倍氯米松二丙酸酯（BDP）时，制剂对包封的影响，使用高密度分散介质重水（D2O）与去离子水（DW）进行比较。采用乳糖一水合物（LMH）、山梨糖醇或 D-甘露醇作为碳水化合物载体（脂质与载体的重量比为 1:5），制备了包含 BDP（脂质相的 2mol%，由大豆卵磷脂（SPC）和胆固醇组成；1:1）的前体脂质体。在优化的 90 分钟离心时间和 15,500g 的离心力下，分离了包封 BDP 的脂质体和未包封（游离）BDP。发现分散介质对分离包封 BDP 的脂质体和未包封药物有很大影响。当使用 DW 时，包封效率值估计高于 95%。相比之下，当使用 DO 作为分散介质时，包封效率分别为 19.69±5.88%、28.78±4.69%和 34.84±3.62%（分别用于基于 LMH、山梨糖醇和 D-甘露醇的前体脂质体）。发现脂质体和 BDP 晶体的大小相似是导致在 DW 中离心时脂质体和游离 BDP 晶体共沉降的原因，从而导致估计的包封效率过高。这通过使用 DO 得到了纠正，这一点通过光学显微镜、核磁共振（NMR）、X 射线衍射（XRD）和包封研究得到了证实。这项研究表明，载体类型对从前体脂质体生成的脂质体中包封 BDP 有显著影响，并且使用 DO 对于准确确定囊泡中类固醇的包封是必要的。
