The incorporation of nitric oxide (NO) photodonors into nontoxic vehicles may allow for the tunable control of topical NO release to treat pathological conditions associated with the impairment of NO production in the dermal vasculature. Pluronic F127 is a PEO-PPO-PEO triblock copolymer that is used as a nontoxic vehicle that undergoes thermally reversible micellization and gelation. In this study, we synthesized a thermally stable flutamide derivative, N-(3-aminopropyl)-3-(trifluoromethyl)-4-nitrobenzenamine (ATN), which is capable of releasing NO upon irradiation with visible light, as shown by real-time chemiluminescence NO detection. We demonstrated that the incorporation of ATN into the hydrophobic nuclei of F127 micelles leads to an enhancement of its photochemical NO release, which is consistent with the photodecomposition route associated with the nitro-to-nitrite photorearrangement of ATN. This mechanism underscores a new role of the F127 micelles as concentrating "nanoreactors" for hydrophobic NO releasing drugs. In this case, this effect may represent a new strategy for enhancing photochemical NO release from ATN, which makes the micellar F127/ATN solutions promising for topical NO application. © 2014 Elsevier B.V.293 6571Nicolas, J., Mura, S., Brambilla, D., MacKiewicz, N., Couvreur, P., Design functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery (2014) Chem. Soc. Rev., 42, p. 1147Basak, R., Bandyopadhyay, R., Encapsulation of hydrophobic drugs in pluronic F127 micelles: Effects of drug hydrophobicity, solution temperature, and pH (2013) Langmuir, 29, p. 4350Alexander, S., Cosgrove, T., Prescott, S.W., Castle, T.C., Flurbiprofen encapsulation using pluronic triblock copolymers (2011) Langmuir, 27, p. 8054Miyazaki, S., Tobiyama, T., Takada, M., Attwood, D., Percutaneous absorption of indomethacin from pluronic F127 gels in rats (1995) J. Pharm. Pharmacol., 47, p. 455Foster, B., Cosgrove, T., Hammouda, B., Pluronic triblock copolymer systems and their interactions with ibuprofen (2009) Langmuir, 25, p. 6760Attwood, D., Collett, J.H., Tait, C.J., The micellar properties of the poly(oxyethylene)-poly(oxypropylene) copolymer Pluronic F127 in water and electrolyte solution (1985) Int. J. Pharm., 26, p. 25Alexandridis, P., Hatton, T.A., Poly(ethylene oxide)-poly(propylene oxide)-poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: Thermodynamics, structure, dynamics, and modeling (1995) Colloids Surf. A: Physicochem. Eng. Asp., 96, p. 1Wanka, G., Hoffmann, H., Ulbricht, W., Phase-diagrams and aggregation behavior of poly(oxyethylene)- poly(oxypropylene)-poly(oxyethylene) triblock copolymers in aqueous-solutions (1994) Macromolecules, 27, p. 4145Dumortier, G., Grossiord, J.L., Agnely, F., Chaumeil, J.C., A review of poloxamer 407 pharmaceutical and pharmacological characteristics (2006) Pharm. Res., 23, p. 2709Escobar-Chávez, J.J., López-Cervantes, M., Naïk, A., Kalia, Y.N., Quintanar-Guerreo, D., Ganem-Quintanar, A., Applications of thermoreversible Pluronic F-127 gels in pharmaceutical formulations (2006) J. Pharm. Pharmaceut. Sci., 9, p. 339Carpenter, A.W., Schoenfisch, M.H., Nitric oxide release: Part II. Therapeutic applications (2012) Chem. Soc. Rev., 41, p. 3742Seabra, A.B., Durán, N., Nitric oxide-releasing vehicles for biomedical applications (2010) J. Mater. Chem., 20, p. 1624Georgii, J.L., Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Topical S-nitrosoglutathione-releasing hydrogel improves healing of rat ischaemic wounds (2011) J. Tissue Eng. Regen. Med., 5, p. 612Seabra, A.B., Fitzpatrick, A., Paul, J., De Oliveira, M.G., Weller, R.A., Topically applied S-nitrosothiol-containing hydrogels as experimental and pharmacological nitric oxide donors in human skin (2004) Br. J. Dermatol., 151, p. 977Seabra, A.B., Martins, D., Simões, M.M.S.G., Da Silva, R., Brocchi, M., De Oliveira, M.G., Antibacterial nitric oxide-releasing polyester for the coating of blood-contacting artificial materials (2010) Artif. Organs, 34, p. 204Riccio, D.A., Schoenfisch, M.H., Nitric Oxide release: Part I. Macromolecular scaffolds (2012) Chem. Soc. Rev., 41, p. 3731Etchenique, R., Furman, M., Olabe, J.A., Photodelivery of nitric oxide from a nitrosothiol-derivatized surface (2000) J. Am. Chem. Soc., 122, p. 3967Shishido, S.M., Seabra, A.B., Loh, W., Ganzarolli De Oliveira, M., Thermal and photochemical nitric oxide release from S-nitrosothiols incorpored in Pluronic F127 gel: Potential uses for local and controlled nitric oxide release (2003) Biomaterials, 24, p. 3543Riccio, D.A., Coneski, P.N., Nichols, S.P., Broadnax, A.D., Schoenfisch, M.H., Photoinitiated nitric oxide-releasing tertiaty S-nitrosothiols-modified xerogels (2012) ACS Appl. Mater. Interfaces, 4, p. 796Georgii, J.L., Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Monte-Alto-Costa, A., Topical S-nitrosoglutathione-releasing hydrogel improves healing of rat ischaemic wounds (2001) J. Tissue Eng. Regen. Med., 5, p. 612Sortino, S., Nanostructured molecular films and nanoparticles with photoactivable functionalities (2008) Photochem. Photobiol. Sci., 7, p. 911Sortino, S., Photoactivated nanomaterials for biomedical release applications (2012) J. Mater. Chem., 22, p. 301Swaminathan, S., Garcia-Amorós, J., Fraix, A., Kandoth, N., Sortino, S., Raymo, F.M., Photoresponsive polymer nanocarriers with multifunctional cargo (2014) Chem. Soc. Rev.Kandoth, N., Mosinger, J., Gref, R., Sortino, S., A NO photoreleasing supramolecular hydrogel with bactericidal action (2013) J. Mater. Chem. B, 1, p. 3458Taladriz-Blanco, P., Pérez-Juste, J., Kandoth, N., Herves, P., Sortino, S., Layer-by-layer assembled gold nanoparticles with a tunable payload of a nitric oxide photocage (2013) J. Colloid Interface Sci., 407, p. 524Callari, F.L., Sortino, S., Amplified nitric oxide photorelease in DNA proximity (2008) Chem. Commun., p. 1971Schmolka, I.R., Astificial Skin, I., Preparation and properties of pluronic F-127 gels for treatment of burns (1972) J. Biomed. Mater. Res., 6, p. 571Coneski, P.N., Schoenfisch, M.H., Nitric oxide release: Part III. Measurement and reporting (2012) Chem. Soc. Rev., 41, p. 3753Marcilli, R.H.M., De Oliveira, M.G., Nitric oxide-releasing poly(vinyl alcohol) film for increasing dermal vasodilation (2014) Colloids Surf. B: Biointerfaces, 116, p. 643Sortino, S., Giuffrida, G.D.Q., Chilemi, R., Petralia, S., Marconi, G., Condorelli, G., Sciuto, S., The photochemistry of flutamide and its inclusion complex with b-cyclodextrin. Dramatic effect of the microenvironment on the nature and on the efficiency of the photodegradation pathways (2001) Photochem. Photobiol., 73, p. 5Sortino, S., Marconi, G., Condorelli, G., New insight on the photoreactivity of the phototoxic anti-cancer flutamide: Photochemical pathways selectively locked and unlocked by structural changes upon drug compartmentalization in phospholipid bilayer vesicles (2001) Chem. Commun., p. 1226Udagawa, C., Fukuyoshi, S., Morimoto, S., Tanimoto, Y., Nakagaki, R., Photochemistry of flutamide in various media: Investigation of the reaction mechanism as revealed by external magnetic field effects on product yields (2011) J. Photochem. Photobiol. A, 226, p. 57