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].
References:
[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.