Thermosensitive sol-gel reversible hydrogels.

Poloxamer 407 copolymer (ethylene oxide and propylene oxide blocks) shows thermoreversible properties, which is of the utmost interest in optimising drug formulation (fluid state at room temperature facilitating administration and gel state above sol-gel transition temperature at body temperature promoting prolonged release of pharmacological agents). Pharmaceutical evaluation consists in determining the rheological behaviour (flow curve or oscillatory studies), sol-gel transition temperature, in vitro drug release using either synthetic or physiological membrane and (bio)adhesion characteristics. Poloxamer 407 formulations led to enhanced solubilisation of poorly water-soluble drugs and prolonged release profile for many galenic applications (e.g., oral, rectal, topical, ophthalmic, nasal and injectable preparations) but did not clearly show any relevant advantages when used alone. Combination with other excipients like Poloxamer 188 or mucoadhesive polymers promotes Poloxamer 407 action by optimising sol-gel transition temperature or increasing bioadhesive properties. Inclusion of liposomes or micro(nano)particles in Poloxamer 407 formulations offers interesting prospects, as well. Besides these promising data, Poloxamer 407 has been held responsible for lipidic profile alteration and possible renal toxicity, which compromises its development for parenteral applications. In addition, new findings have demonstrated immuno-modulation and cytotoxicity-promoting properties of Poloxamer 407 revealing significant pharmacological interest and, hence, human trials are in progress to specify these potential applications.

A Review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics

Hydrogels for protein delivery.

The use of mucoadhesive polymers in buccal drug delivery.

Poly(ethylene oxide)–poly(propylene oxide) block copolymer micelles as drug delivery agents: Improved hydrosolubility, stability and bioavailability of drugs

Pluronic F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insulin.

Enhanced rectal absorption of insulin-loaded Pluronic F-127 gels containing unsaturated fatty acids.

Enhanced colonic and rectal absorption of insulin using a multiple emulsion containing eicosapentaenoic acid and docosahexaenoic acid.

We investigated the effect of fatty acids such as stearic acid (SA, 18:0), oleic acid (OA, 18:1), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6) on a dipalmitoylphosphatidylcholine (DPPC) bilayer by determining the phase transition temperature, fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH), and detergent insolubility. Treatment with unsaturated fatty acid broadened and shifted the phase transitions of the DPPC bilayer to a lower temperature. The phase transition temperature and the value of fluorescence anisotropy of DPH at 37 degrees C decreased progressively with increasing treatment amounts of unsaturated fatty acid. A large amount of the DPPC bilayer treated with unsaturated fatty acid was dissolved in Triton X-100, obtaining a low level of detergent insolubility. These modifications of the bilayer physical properties were most pronounced with DHA and EPA treatment. These data show that unsaturated fatty acids, particularly DHA and EPA, induce a marked change in the lipid bilayer structure. The composition of fatty acids in the DPPC bilayer was similar after treatment with various unsaturated fatty acids, suggesting that the different actions of unsaturated fatty acids are attributed to change in the molecular structure (e.g., kinked conformation by double bonds). We further explored the change in physical properties induced by fatty acids dispersed in a water-in-oil-in-water multiple emulsion and found that unsaturated fatty acids acted efficiently on the DPPC bilayer, even when incorporated in emulsion form.

Docosahexaenoic Acid and Eicosapentaenoic Acid Induce Changes in the Physical Properties of a Lipid Bilayer Model Membrane

Enhanced enteral bioavailability of vancomycin using water‐in‐oil‐in‐water multiple emulsion incorporating highly purified unsaturated fatty acid

Shinji Tokiwa

Papers

Pluronic F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insulin.

Enhanced rectal absorption of insulin-loaded Pluronic F-127 gels containing unsaturated fatty acids.

Enhanced colonic and rectal absorption of insulin using a multiple emulsion containing eicosapentaenoic acid and docosahexaenoic acid.

Docosahexaenoic Acid and Eicosapentaenoic Acid Induce Changes in the Physical Properties of a Lipid Bilayer Model Membrane

Enhanced enteral bioavailability of vancomycin using water‐in‐oil‐in‐water multiple emulsion incorporating highly purified unsaturated fatty acid