Towards the Development of Long Circulating Phosphatidylserine (PS)- and Phosphatidylglycerol (PG)-Enriched Anti-Inflammatory Liposomes: Is PEGylation Effective?
Towards the Development of Long Circulating Phosphatidylserine (PS)- and Phosphatidylglycerol (PG)-Enriched Anti-Inflammatory Liposomes: Is PEGylation Effective?
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DOI：
10.3390/pharmaceutics13020282
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发表时间：
2021-02-19
期刊：
影响因子：
5.4
通讯作者：
Lucas H
中科院分区：
文献类型：
--
作者：
Klein ME;Rieckmann M;Sedding D;Hause G;Meister A;Mäder K;Lucas H
磷脂酰丝氨酸（PS）和磷脂酰甘油（PG）是具有抗炎和免疫调节活性的内源性磷脂。潜在的临床应用需要明确的系统，并且对于若干应用，需要长的循环时间。因此，我们的目标是开发具有内在抗炎活性的长循环脂质体。因此，产生富含PS和PG的脂质体，而磷脂酰胆碱（PC）脂质体用作对照。将脂质体配制为常规制剂或PEG化制剂。它们的直径低于150 nm，窄的尺寸分布和组合物依赖的表面电荷。通过体内荧光成像（FI）非侵入性评估药代动力学，并在切除的器官中离体评估2天。常规配制的PC脂质体从循环中快速清除，而PEG化导致脂质体循环延长，在大多数器官中稳健分布。相比之下，PS和PG脂质体，作为常规或PEG化制剂，均被快速清除。非PEG化PS和PG脂质体几乎完全在肝脏中蓄积。相比之下，PEG化PS和PG脂质体主要在肝脏和脾脏中观察到。总之，聚乙二醇化的PS和PG脂质体不能有效延长循环时间，但在脾脏中引起更高的摄取。
The anionic phospholipids (PLs) phosphatidylserine (PS) and phosphatidylglycerol (PG) are endogenous phospholipids with anti-inflammatory and immunomodulatory activity. A potential clinical use requires well-defined systems and for several applications, a long circulation time is desirable. Therefore, we aimed the development of long circulating liposomes with intrinsic anti-inflammatory activity. Hence, PS- and PG-enriched liposomes were produced, whilst phosphatidylcholine (PC) liposomes served as control. Liposomes were either formulated as conventional or PEGylated formulations. They had diameters below 150 nm, narrow size distributions and composition-dependent surface charges. Pharmacokinetics were assessed non-invasively via in vivo fluorescence imaging (FI) and ex vivo in excised organs over 2 days. PC liposomes, conventionally formulated, were rapidly cleared from the circulation, while PEGylation resulted in prolongation of liposome circulation robustly distributing among most organs. In contrast, PS and PG liposomes, both as conventional or PEGylated formulations, were rapidly cleared. Non-PEGylated PS and PG liposomes did accumulate almost exclusively in the liver. In contrast, PEGylated PS and PG liposomes were observed mainly in liver and spleen. In summary, PEGylation of PS and PG liposomes was not effective to prolong the circulation time but caused a higher uptake in the spleen.
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