Poloxamer

The word poloxamer was coined by BASF inventor, Irving Schmolka, who received the patent for these materials in 1973.

This aggregation is driven by the dehydration of the hydrophobic polyoxypropylene block that becomes progressively less soluble as the polymer concentration or temperature increases.

Thus, the core of the aggregates is made from the insoluble blocks (polyoxypropylene) while the soluble portion (polyoxyethylene) forms the shell of the micelles.

The mechanisms on the micellization at equilibrium have shown to depend on two relaxation times: (1) the first and fastest (tens of the microseconds scale) corresponds to the unimers exchange between micelles and the bulk solution and follows the Aniansson-Wall model (step-by-step insertion and expulsion of single polymer chains),[11] and (2) the second and much slower one (in the millisecond range) is attributed to the formation and breakdown of whole micellar units leading to the final micellar size equilibration.

The final geometry will depend on the entropy costs of stretching the blocks, which is directly related to their composition (size and polyoxypropylene/polyoxyethylene ratio).

[13] With higher increments of the temperature and/or concentration, other phenomena can occur such as the formation of highly ordered mesophases (cubic, hexagonal and lamellar).

Eventually, a complete dehydration of the polyoxypropylene blocks and the collapse of the polyoxyethylene chains will lead to clouding and/or macroscopic phase separation.

Different phase diagrams characterizing all these transitions have been constructed for most poloxamers using a great variety of experimental techniques (e.g. SAXS, Differential scanning calorimetry, viscosity measurements, light scattering).

[16] Work led by Kabanov has recently shown that some of these polymers, originally thought to be inert carrier molecules, have a very real effect on biological systems independently of the drug they are transporting.

The poloxamers have also been shown to enhance proto-apoptotic signaling, decrease anti-apoptoic defense in MDR cells, inhibit the glutathione/glutathione S-transferase detoxification system, induce the release of cytochrome C, increase reactive oxygen species in the cytoplasm, and abolish drug sequestering within cytoplasmic vesicles.