S-nitrosoglutathione incorporated in poly(ethylene glycol) matrix: potential use for topical nitric oxide delivery.
Incorporation of nitric oxide (NO) donors in non-toxic polymeric matrices can be a useful strategy for allowing topical NO delivery. We have incorporated the NO-donor S-nitrosoglutathione (GSNO) into a liquid poly(ethylene glycol) (PEG)/H2O matrix through the S-nitrosation of GSH by a NO/O2 gas mixture. Kinetic measurements of GSNO decomposition associated with NO release were performed at 25, 35, and 45 degrees C in the dark and under irradiation with UV/Vis light, lambda>480 nm and lambda=333 nm. NO release from the liquid matrix to the gas phase was confirmed by mass spectrometry. The PEG/H2O matrix stabilizes GSNO leading to expressive reductions in the initial rates of thermal and photochemical NO release, compared to aqueous GSNO solution. This matrix effect is assigned to diffusional constrains imposed on the escape of the NO and GS radicals formed in the solvent cage. This effect allows the storage of PEG-GSNO formulations for extended periods (more than 65 days at freezer) with negligible decomposition. PEG-GSNO formulation seems therefore to be applicable in topical NO delivery and GSNO displays potential as a percutaneous absorption enhancer. Moreover, the rate of NO release can be locally increased by irradiation with visible light.
Seabra
Amedea Barozzi
AB
Departamento de Físico-Química, Instituto de Química, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil.
de Souza
Gabriela Freitas Pereira
GF
da Rocha
Lilian Lúcia
LL
Eberlin
Marcos Nogueira
MN
de Oliveira
Marcelo Ganzarolli
MG
D000287:Administration, Topical; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D007700:Kinetics; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000378:metabolism*; D010777:Photochemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D026422:S-Nitrosoglutathione / Q000737:chemistry / Q000378:metabolism*; D012996:Solutions; D013057:Spectrum Analysis; D013696:Temperature
D020030:Nitric Oxide Donors; D012996:Solutions; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D026422:S-Nitrosoglutathione