Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)A better comprehension of the prilocaine (PLC)-beta-cyclodextrin (beta-CD) complex liberation to membranes was provided by studying the architectural supramolecular arrangements of PLC, beta-CD and egg phosphatidylcholine (EPC) liposomes, a membrane model. The topologies and possible interactions of mixtures of PLC, beta-CD and EPC liposomes were investigated by nuclear magnetic resonances combining experimental H-1-NMR (1D ROESY, STD and DOSY) at different pHs. The results indicate that in the mixture PLC/beta-CD/EPC at pH 10 the PLC molecules are almost totally embedded into the liposomes and little interaction was observed between PLC and beta-CD. However, at pH 5.5 not only was PLC imbedded in the EPC bilayer, but PLC was also interacting with beta-CD. These results were rationalized as a spontaneous PLC release from beta-CD to liposomes vesicles, whereas the PLC/EPC complex formation was higher at pH 10 than pH 5.5. Copyright (C) 2011 John Wiley & Sons, Ltd.496295300Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)ANPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)