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INTRODUÇÃONa fase atual da vida social brasileira existem obstáculos para a criação de um sistema eficaz de proteção e promoção da saúde, mas também um promissor despertar da consciência popular em torno do assunto.A vida, a saúde e o bem-estar material e espiritual são requisitos elementares da condição humana, e a carência de qualquer desses requisitos suprime ou, pelo menos, prejudica essa condição genuinamente humana do ser. O direito de todas as crianças à vida, à saúde, ao bem-estar e a uma formação integral está estreitamente vinculado às condições gerais econômicas, sociais e legais imperantes na sociedade (1).Desde o aparecimento da vida sobre a terra, a doença a ela esteve associada, portanto antiga como a própria vida, porque é um atributo da vida. Como fenômeno biológico, as causas da doença estão enraiza-

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Binding and localization of the vasodilator and antitumor drug coactivator dipyridamole (DIP) and one of its derivatives, RA25, to phospholipid vesicles of DMPC (dimyristoylphosphatidylcholine) and DPPC (dipalmitoylphosphatidylcholine) was studied using fluorescence spectroscopy as well as quenching of fluorescence. The analysis of fluorescence data indicates that neutral dipyridamole binds to the phospholipids in their liquid crystalline phase with an association constant of 950 M(-1) and 1150 M(-1) to DMPC and DPPC, respectively. Protonation of DIP leads to a 3-fold reduction of the association constant. For the gel phospholipid phase, the binding is smaller (a factor of 2), independently of pH, suggesting that the more flexible lipid packing in the liquid crystalline phase facilitates the binding of the drug. The association constant of RA25 neutral form is considerably lower than for DIP, being around 295 M(-1). Fluorescence quenching with nitroxides TEMPO and stearic acid doxyl derivatives suggests the localization of DIP to be closer to the 5th carbon of alkyl chain. The quenching effect of 5-DSA below the lipid phase transition suggests that a strong static quenching may be operative. The quenching effect of 16-DSA is almost as great as that for 5-DSA below the phase transition, being even higher above the phase transition. This effect is probably due to the trans-gauche isomerization of the stearic acid nitroxide, making the encounter of its paramagnetic fragment with the DIP chromophore possible. Our data are consistent with DIP location close to the bilayer surface in the border of hydrophobic-polar heads interface which is similar to the data in micellar systems. In the case of RA25, the drug is in the outer part of the head group interface being much exposed to the aqueous phase and being significantly less accessible to the membrane nitroxide quenchers.