Pluronic solubilization

Nonionic surfactants such as polyoxyethylated fatty alcohols (such as Emul-phor ON-870 from GAP), alkyl phenyl polyethylene glycol ethers (such as the Tergitols from Union Carbide) and polyoxyethylated octylphenol may be used as protective colloids along with anionic surfactants or, in some cases, as emulsifiers in their own right. The block copolymers of polyoxyethylene and polyoxypropylene (Pluronics) solubilized vinyl acetate. Polymerization takes place at the interface of the surfactant-monomer droplet and the aqueous phase [151]. 

Lin and Yang (1987) also calculated the thermodynamic parameters of diazepam for micellar solubilization in Pluronic surfactant solutions at different temperatures (Table 13.4). For all systems, AG was negative, indicating micellar solubilization was spontaneous. The sign of entropy has been associated with the location of solubilized molecules within the micelles. Positive values have been observed for molecules embedded in the micelle center and negative values for adsorption of the molecules on the micelle surface. The results in this paper indicate that in the F-108 and F-88 Pluronics, diazepam molecules can penetrate into the micelle interior, whereas for F-68 and lower concentrations of F-88, diazepam is adsorbed on the micelle surface without penetration into the micellar core. 

Thermodynamic Parameters for the Solubilization of Diazepam by Pluronic Surfactants... 

Solubilization oftropicamide, a poorly water-soluble mydriatic/cycloplegicdrug, by poloxamers or Pluronics was studied (Saettone et al., 1988). The polymers evaluated as solubilizers for the drug included L-64, P-65, F-68, P-75, F-77, P-84, P-85, F-87, F-88, and F-127. The authors measured a range of physicochemical properties, such as solubility oftropicamide in polymer solutions, partition coefLcient of the drug between isopropyl myristate and copolymer solutions, critical micelle concentration of the copolymers, and viscosity of the copolymeric solutions containing tropicamide. 

The solubility and release of naproxen from Pluronic PF-127 micelles were studied as a function of temperature and pH by Suh and Jun (1996). The solubility of the drug at pH 2 was signiLcantly increased as a linear function of PF-127 concentrations for three temperatures. Naproxen was highly entrapped by the micelles as indicated by large partition coefLcient. The micellar solubilization was a spontaneous (AG 0) and exothermic (AH< 0) process that resulted in a less ordered state (AS > 0). In the presence of PF-127, the release of naproxen was sustained at pH 2 and inversely proportional to the surfactant concentration. In contrast, at pH 7, PF-127 had little effect on the membrane transport of naproxen. The release of naproxen from the PF-127 gel into isopropanol myristate was also found to be dependent on the medium pH with the highest release observed at pH 6.3. 

Pandya, K., P. Bahadur,T. N. Nagar, andA. Bahadur. 1993. Micellar and solubilizing behavior of Pluronic L64 in water.Coll. Surf. A Phys. EngTO 219-227. 

Sek, L., et al., Examination of the impact of a range of pluronic surfactants nmvtfo solubilization behavior and oral bioavailability of lipidic formulations of atovaquodepharm. Pharmacql 58,... 

Lipids also can be beneficial for cells in culture, since some substances absorbed by the cells need to be solubilized in lipids, or in some cases the toxicity of compounds may be reduced by complexation with lipids. The absence of essential lipids such as linoleic acid, lecithin, cholesterol, ethanolamine, or phosphorylcholine can result in the decrease of cloning efficiency and in reduction in the size of colonies, as shown for insect cells by Echalier (1997). However, one of the difficulties in supplying lipids at reasonable concentrations is their low solubility. To circumvent this limitation, lipids can be emulsified with complexing agents such as Pluronic F68 or cyclodextrin (Maiorella et al., 1998). 

These are stable micelles that are formed with polymeric surfactants. Amphiphilic block copolymers such as the pluronics (polyoxyethylene-polyoxypropylene block copolymers) are able to self-assemble into polymeric micelles and hydrophobic drugs may be solubilized within the core of the micelle or, alternatively, conjugated to the micelle-forming polymer. Although micelles are rather dynamic systems that continuously exchange units between the micelle structure and the free units in solution, those composed of polyoxyethylene - poly(aspartic acid) have been found sufficiently... 

Solubilizers (e.g., organic solvents, detergents, Pluronics) are often used to solubilize drugs in aqueous solution without considering their effects on biological systems, such as (i) lipid membranes and (n) multidrug resistance (MDR) efflux transporters (e.g., Pgp or MDRl). 

Pluronic P85 was also reported to cause a higher degree of alteration in the P-gp functions than MRP2 and MRPl in ATPase assay of P-gp, MRPl, and MRP2 and inhibition assays with their substrates, vinblastine, and leucotriene-C4 (Batrakova et al., 2004). Cremophor EL (cremophor) is a nonionic solubilizer and emulsifier used for some hydrophobic drugs and fat-soluble vitamins. In a Phase I trial of cremophor as a 6-h infusion every 3 weeks performed with bolus doxorubicin (50mg/m ), the AUC of doxorubicin increased from 1448 (CV of 24%) to 1786 h ng/mL (CV of 15%) in the presence of cremophor, whereas the AUC of doxorubicinol increased from 252 (CV of 42%) to 486 (CV of 22%) h ng/mL. Such interactions can be due to decreased clearance of doxorubicin 612 (CV of 29%) to 477 (CV of 15%)... 

Page M, Alakhov VY. Elimination of P-gp-mediated multidrug resistance by solubilization in Pluronic micelles. Proceedings of the Annual Meeting of the American Association for Cancer Research (AACR), Philadelphia, PA, USA. Vol. 33, 1992. 

CAU Causse, J., Lagerge, S., Menorval, L.C. de, and Faure, S., Micellar solubilization of tributylphosphate in aqueous solutions of Pluronic block copolymers Part I. Effect of the copolymer stmcture and temperature on the phase behavior, J. Colloid Interface Sci., 300, 713, 2006. 

Pluronic poloxamers can be suitable carrier materials for this purpose due to their capacity to enhance the absorption of water-insoluble compounds by formation of micelles in aqueous environment that can host such hydrophobic compounds. Different authors have described the formation of quercetin-loaded Pluronic micelles by thin-film hydration methods and have shown that the resulting micelles enhanced the solubilization of the active compound. Ghanem et al. described the encapsulation of quercetin in Pluronic F127 via spray drying. ... 

---