Poloxamer 188 (P188) as a Membrane Resealing Reagent in Biomedical Applications

Abstract

Maintenance of the integrity of the plasma membrane is essential for maintenance of cellular function and prevention of cell death. Since the plasma membrane is frequently exposed to a variety of mechanical and chemical insults the cell has evolved active processes to defend against these injuries by resealing disruptions in the plasma membrane. Cell membrane repair is a conserved process observed in nearly every cell type where intracellular vesicles are recruited to sites of membrane disruption where they can fuse with themselves or the plasma membrane to create a repair patch. When disruptions are extensive or there is an underlying pathology that reduces the membrane repair capacity of a cell this defense mechanism may prove insufficient and the cell could die due to breakdown of the plasma membrane. Extensive loss of cells can compromise the integrity and function of tissues and leading to disease. Thus, methods to increase membrane resealing capacity could have broad utility in a number of disease states. Efforts to find reagents that can modulate plasma membrane reseal found that specific tri-block copolymers, such as poloxamer 188 (P188, or Pluronic F68), can increase the structural stability and resealing of the plasma membrane. Here we review several current patents and patent applications that present inventions making use of P188 and other copolymers to treat specific disease states such as muscular dystrophy, heart failure, neurodegenerative disorders and electrical injuries, or to facilitate biomedical applications such as transplantation. There appears to be promise for the application of poloxamers in the treatment of various diseases, however there are potential concerns with toxicity with long term application and bioavailability in some cases.

Intraneuronal Amylin Deposition, Peroxidative Membrane Injury and Increased IL-1β Synthesis in Brains of Alzheimer’s Disease Patients with Type-2 Diabetes and in Diabetic HIP Rats

“…8A). Incorporation of aggregated amylin in cell membranes was then prevented by pre-treating isolated control neurons with 50 μM poloxamer 188, a surfactant that stabilizes the lipid bilayer through hydrophobic interactions [36, 37]. Surfactant molecules (S) blocked amylin-induced lipid peroxidation (Fig.…”

Behavior of P85 and P188 Poloxamer Molecules: Computer Simulations Using United-Atom Force-Field

“…During all the runs we performed we did not observe a P85 translocation to the other side of the membrane, since such a translocation would require overcoming a significant free energy barrier. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 It is known that poloxamers such as P188 have membrane sealing properties and can be used as agents that restore the integrity of a damaged membrane [61][62][63] . The molecular details of how this occurs are not known and molecular dynamics simulations could potentially provide molecular resolution pictures of the possible mechanism by which these molecules work.…”

PEO–PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture

“…Their amphiphilic nature provides these molecules with remarkable properties and potential for biomedical and pharmaceutical applications. A representative class of amphiphilic block copolymers is triblock copolymers formed from poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), also known as Pluronics or poloxamers 1 . Poloxamers have been used as versatile biomaterials such as thermosensitive hydrogels 2,3 , drug delivery carriers 4,5 , and chemosensitization agents for cancer therapy 6–8 .…”