Poloxamer
Poloxamers are nonionic triblock copolymers composed of a central hydrophobic chain of polyoxypropylene (poly(propylene oxide)) flanked by two hydrophilic chains of polyoxyethylene (poly(ethylene oxide)). The word "poloxamer" was coined by the inventor, Irving Schmolka, who received the patent for these materials in 1973.[1] Poloxamers are also known by the trade name Pluronics.[2]
Because the lengths of the polymer blocks can be customized, many different poloxamers exist that have slightly different properties. For the generic term "poloxamer", these copolymers are commonly named with the letter "P" (for poloxamer) followed by three digits, the first two digits x 100 give the approximate molecular mass of the polyoxypropylene core, and the last digit x 10 gives the percentage polyoxyethylene content (e.g., P407 = Poloxamer with a polyoxypropylene molecular mass of 4,000 g/mol and a 70% polyoxyethylene content) . For the Pluronic tradename, coding of these copolymers starts with a letter to define its physical form at room temperature (L = liquid, P = paste, F = flake (solid)) followed by two or three digits, The first digit (two digits in a three-digit number) in the numerical designation, multiplied by 300, indicates the approximate molecular weight of the hydrophobe; and the last digit x 10 gives the percentage polyoxyethylene content (e.g., L61 = Pluronic with a polyoxypropylene molecular mass of 1,800 g/mol and a 10% polyoxyethylene content). In the example given, poloxamer 181 (P181) = Pluronic L61.
Uses of poloxamers
Because of their amphiphilic structure, the polymers have surfactant properties that make them useful in industrial applications. Among other things, they can be used to increase the water solubility of hydrophobic, oily substances or otherwise increase the miscibility of two substances with different hydrophobicities. For this reason, these polymers are commonly used in industrial applications, cosmetics, and pharmaceuticals. They have also been used evaluated for various drug delivery applications and were shown to sensitize drug resistant cancers to chemotherapy.
In bioprocess applications, pluronic is also used in cell culture media for its cell cushioning effects because its addition leads to less stressful shear conditions for cells in reactors.
Biological Effect Of Poloxamers
Originally thought to be inert carrier molecules work led by Kabanov has recently shown that some of these polymers have a very real effect on biological systems independently of the drug they are transporting. The poloxamers have been shown to incorporate into cellular membranes affecting the microviscosity of the membranes.
Effect on Multi Drug Resistant Cancer Cells
Poloxamers have been show to preferentially target cancer cells, due to differences in the membrane of these cells when compared to non cancer cells. Poloxamers have also been shown to inhibit MDR proteins and other drug efflux transporters on the surface of cancer cells, the MDR proteins are responsible for the efflux of drugs from the cells and hence increase the susceptibility of cancer cells to chemotherapeutic agents such as doxycycline.
Another effect of the polymers upon cancer cells in the inhibition of the Production of ATP in multi-drug resistant (MDR) cancer cells. The polymers seem to inhibit respatory proteins I and IV, the effect on respiration seems to be selective for MDR cancer cells, which may be explained by the difference in fuel sources between MDR and sensitive cells (fatty acids and glucose respectively).
The poloxamers have also been shown to; enhance proto-apoptotic signaling, and decrease anti apoptoic defence in MDR cells, inhibit the glutathione/glutathione S-transferase detoxification system, induce the release of cytochrome C and increase reactive oxygen species in the cytoplasm and abolish drug sequesteratrion within cytoplasmic vesicles.
Interestingly the polymers seem to have the greatest effect when absorbed by the cell as a unimer rather than as a micelle
Effect on Nuclear Factor kappa B
Certain poloxamers such as P85 have been shown not only to be able to transport target genes to target cells, but also to increase gene expression. Certain poloxamers, such as P85 and L61, have also been shown to stimulate transcription of NF kappaB genes, although the mechanism by which this is achieved is currently unknown, bar that P85 has been shown to induce phosphorylation of the Inhibitory kappa.
References
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<references />, or <references group="..." />Bartrakova & Kabanov (2008) Pluronic block copolymers: Evolution of drug delivery concept from inert nanocarriers to biological response modifiers. Journal of Controlled Release. 130 98-106
See also
Karmarkar AB, Gonjari ID, Hosmani AH. Poloxamers and their applicationsde:Poloxamere ru:Плюроники
zh:泊洛沙姆- ↑ US 3740421
- ↑ "BASF - Product information the chemicals catalog - Pluronics". BASF Corporation Website. Retrieved 2008-12-09.
