Long-term storage of lyophilized liposomal formulations.
Long-term storage of lyophilized liposomal formulations.
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DOI：
10.1002/jps.24171
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发表时间：
2014-12
影响因子：
3.8
通讯作者：
Anchordoquy, Thomas J.
中科院分区：
文献类型：
--
作者：
Payton, Nicole M.;Wempe, Michael F.;Xu, Yemin;Anchordoquy, Thomas J.
由于含有多重不饱和脂质的水性脂质体制剂易于化学降解，因此这些制剂通常被冻干。尽管化学稳定性有限，但近年来，人们对使用多重不饱和脂质促进细胞内递送的兴趣大大增加。当前研究的目的是检查含有不饱和度水平增加的脂质的冻干制剂的长期储存稳定性，以及可用于提高稳定性的各种策略。将含有 1,2-二亚油酰-sn-甘油-3-磷酸胆碱 (DLPC)、1,2-二亚油酰-sn-甘油-3-磷酸胆碱 (DLinPC) 或 1,2-二油酰-sn-甘油-3-磷酸胆碱 (DOPC) 的水性脂质-海藻糖制剂冻干并储存在 4°C 至60°C。我们观察到，随着储存温度和不饱和度水平的增加，脂质降解率增加。即使是市售的最干净的糖也含有铁污染物，并且观察到这些铁污染物的螯合显着提高了 DLPC 在储存过程中的稳定性。然而，配方中所含糖的玻璃化转变温度、冻干前水性样品中氧的减少、辅助脂质（即胆固醇）的包含以及冷冻速率并没有显着提高稳定性。
Because aqueous liposomal formulations containing multiply unsaturated lipids are susceptible to chemical degradation, these formulations are often lyophilized. Despite their limited chemical stability, interest in the use of multiply unsaturated lipids to promote intracellular delivery has increased considerably in recent years. The goal of the current study was to examine the long term storage stability of lyophilized formulations containing lipids with increasing levels of unsaturation, and various strategies which can be employed to improve stability. Aqueous lipid-trehalose formulations containing 1,2-dilinolenoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLinPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) were lyophilized and stored at temperatures ranging from 4°C to 60°C. We observed that the lipid degradation rate increased as the storage temperature and unsaturation level were increased. Even the cleanest sugars which are available commercially contain iron contaminants, and it was observed that the chelation of these iron contaminants significantly improved the stability of DLPC during storage. However, the glass transition temperature of the sugar which was included in the formulation, the reduction of the oxygen in the aqueous sample prior to lyophilization, the inclusion of helper lipids (i.e., cholesterol), and the rate of freezing did not significantly improve stability.
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影响因子：
6.1
作者：
Carvajal, Ana Karina;Rustad, Turid;Storro, Ivar
通讯作者：
Storro, Ivar
影响因子：
3.9
作者：
LABUZA, TP;CHOU, HE
通讯作者：
CHOU, HE
影响因子：
1.9
作者：
COSGROVE, JP;CHURCH, DF;PRYOR, WA
通讯作者：
PRYOR, WA
影响因子：
4.1
作者：
FRANKEL, EN
通讯作者：
FRANKEL, EN
影响因子：
8.8
作者：
Andersen, AB;Risbo, J;Skibsted, LH
通讯作者：
Skibsted, LH