Agradecimentos: The authors are thankful to CAPES (Coordination for the Improvement of Higher Education Personnel), CNPq (National Counsel of Technological and Scientific Development, (Process n° 448908/2014-0); (Gredson Keiff Souza, Process n° 150270/2021-6); (Anita Jocelyne Marsaiole Process n° 307885/2013-5; FAPESP-Research Support Foundation of the State of São Paulo, 2018/07078-0), and to the Laboratory of Nuclear Magnetic Resonance, State University of Londrina (UEL) for the support in the analysis. This research was funded by MCTI/CNPq 14/2014, process number 448908/2014-0 Ver menos

Abstract: The drugs delivery system in the treatment of diseases has advantages such as reduced toxicity, increased availability of the drug, etc. Therefore, studies of the supramolecular interactions between local anesthetics (LAs) butamben (BTB) or ropivacaine (RVC) complexed with 2-hydroxypropyl-ß-cyclodextrin (HP-ßCD) and carried in Stealth liposomal (SL) are performed. 1H-NMR nuclear magnetic resonance (DOSY and STD) were used as the main tools. The displacements observed in the 1H-NMR presented the complexion between LAs and HP-ßCD. The diffusion coefficients of free BTB and RVC were 7.70 × 10-10 m2 s-1 and 4.07 × 10-10 m2 s-1, and in the complex with HP-ßCD were 1.90 × 10-10 m2 s-1 and 3.64 × 10-10 m2 s-1, respectively, which indicate a strong interaction between the BTB molecule and HP-ßCD (98.3% molar fraction and Ka = 72.279 L/mol). With STD-NMR, the encapsulation of the BTB/HP-ßCD and RVC/HP-ßCD in SL vesicles was proven. Beyond the saturation transfer to the LAs, there is the magnetization transfer to the hydrogens of HP-ßCD. BTB and RVC have already been studied in normal liposome systems; however, little is known of their behavior in SL Ver menos