Poloxamer 188 (P188, vepoloxamer) is a triblock copolymer of the form polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO). The center PPO block is hydrophobic, and the side PEO blocks are hydrophilic, resulting in surface-active properties. Poloxamer 188 has been used in the pharmaceutical industry as an excipient in various formulations and drug delivery systems [1].
Poloxamer 188 enhances survival of red blood cells (RBCs) by increasing the stability and decreasing the fragility of the membrane [2]. Poloxamer 188 arrested the G2/M phase of the cell cycle in the K562 BCR-ABL-mediated CML cell line [3].
Poloxamer 188 is effective in recovery of damaged cell membrane on muscle cells after electroshock [4], neurons after trauma [5], and fibroblasts [6] after heat shock. Poloxamer 188 also reduces the rigidity of sickled erythrocytes and contributes to the resolution of symptoms of vaso-occlusive crisis [7] in patients with sickle cell disease. The cell protective effect of Poloxamer 188 is not only related to its action on cell membrane integrity but perhaps to some other additional mechanisms that have been described. Antiapoptotic effect of Poloxamer 188 has been shown on neurons after trauma which is related to an inhibition of the activation of proapoptotic p38 [7]. Poloxamer 188 prevents blood-brain barrier disruption through nuclear factor kappa B (NF-κB)-matrix metalloproteinases (MMPs)-mediated tight junction protein degradation by decreasing the level of MMP2, MMP9, and NF-KB p65 [8].
参考文献:
[1]. T. Wang, A. Markham, S.J. Thomas, et al. Solution stability of poloxamer 188 under stress conditions. J Pharm Sci, 108 (2019), pp. 1264-1271
[2]. Baek EJ, Kim HS, Kim JH, Kim NJ, Kim HO. Stroma-free mass production of clinical-grade red blood cells (RBCs) by using poloxamer 188 as an RBC survival enhancer. Transfusion. 2009;49(11):2285-2295.
[3]. Aoki N, Tamura M, Ohyashiki JH, Sugaya M, Hisatomi H. Poloxamer 188 enhances apoptosis in a human leukemia cell line. Mol Med Rep. 2010;3(4):669-672.
[4]. Lee RC, River LP, Pan FS, Ji L, Wollmann RL. Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. Proc Natl Acad Sci U S A. 1992;89(10):4524-4528.
[5]. Serbest G, Horwitz J, Jost M, Barbee K. Mechanisms of cell death and neuroprotection by poloxamer 188 after mechanical trauma. FASEB J. 2006;20(2):308-310.
[6]. Merchant FA, Holmes WH, Capelli-Schellpfeffer M, Lee RC, Toner M. Poloxamer 188 enhances functional recovery of lethally heat-shocked fibroblasts. J Surg Res. 1998;74(2):131-140.
[7]. Orringer EP, Casella JF, Ataga KI, et al. Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: a randomized controlled trial. JAMA. 2001;286(17):2099-2106.
[8]. Wang T, Chen X, Wang Z, et al. Poloxamer-188 can attenuate blood-brain barrier damage to exert neuroprotective effect in mice intracerebral hemorrhage model. J Mol Neurosci. 2015;55(1):240-250.
泊洛沙姆 188（P188，维泊洛沙姆）是聚环氧乙烷-聚环氧丙烷-聚环氧乙烷 (PEO-PPO-PEO) 形式的三嵌段共聚物。中心 PPO 嵌段是疏水的，侧边的 PEO 嵌段是亲水的，从而具有表面活性。泊洛沙姆 188 已在制药行业用作各种制剂和药物递送系统的赋形剂[1]。
泊洛沙姆 188 通过增加红细胞 (RBC) 的存活率来提高红细胞 (RBC) 的存活率稳定性和降低膜的脆性[2]。泊洛沙姆 188 阻滞 K562 BCR-ABL 介导的 CML 细胞系 [3] 细胞周期的 G2/M 期。
泊洛沙姆 188 可有效修复受损细胞电击后肌肉细胞上的膜 [4]、创伤后神经元 [5] 和热休克后成纤维细胞 [6] 上的膜。 Poloxamer 188 还可以降低镰状红细胞的硬度，有助于缓解镰状细胞病患者的血管闭塞危象症状[7]。泊洛沙姆 188 的细胞保护作用不仅与其对细胞膜完整性的作用有关，而且可能与已描述的其他一些机制有关。 Poloxamer 188 的抗凋亡作用已在创伤后的神经元中显示出来，这与抑制促凋亡 p38 的激活有关[7]。泊洛沙姆 188 通过核因子 kappa B (NF-κB)-基质金属蛋白酶 (MMP) 通过降低 MMP2、MMP9 和 NF-KB p65 的水平介导的紧密连接蛋白降解来防止血脑屏障破坏 [ 8].
| Cell experiment [1]: | |
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Cell lines |
The K562, HL60, NALM-6 and Molt-4 cell lines, Peripheral blood mononuclear cells (PBMC) |
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Preparation Method |
The cells with Poloxamer 188 exhibited a detectable apoptosis signal with Annexin V. The cells were treated with 6% Poloxamer 188 or PEG for 48 h. |
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Reaction Conditions |
6% Poloxamer 188 for 48 h. |
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Applications |
When the K562 cell line was incubated with Poloxamer 188, it was synchronized in the G2/M phase of the cell cycle, none of the cell lines incubated with PEG exhibited a detectable apoptosis signal or experienced changes in the state of their cell cycle. T lymphocytes derived from healthy volunteers incubated with Poloxamer 188 or PEG exhibited no changes in the apoptosis signal or the state of the cell cycle. |
| Animal experiment [2]: | |
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Animal models |
Male ICR mice |
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Preparation Method |
Poloxamer 188 was dissolved in normal saline. After intracerebral hemorrhage (ICH) induction, animals were randomly selected and treated with either 3 or 12 mg poloxamer 188 in 400 μl saline. All treatments were administered as the tail intravenous injection at 1 h after surgery. Sham and vehicle animals received an equivalent volume of saline, as given to animals in the intervention groups (400 μl). |
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Dosage form |
Intravenous injection, 3 or 12 mg |
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Applications |
Injury volume was assessed at poloxamer 188 treated 24 and 72 h post ICH. Quantification of brain injury showed that mice administered poloxamer 188 (12 mg) had significantly reduced injury volume compared with the vehicle-treated groups at 24 and 72 h after ICH |
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参考文献: [1]: Aoki N, Tamura M, Ohyashiki JH, Sugaya M, Hisatomi H. Poloxamer 188 enhances apoptosis in a human leukemia cell line. Mol Med Rep. 2010;3(4):669-672. |
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