| Texto completo | |
| Autor(es): |
Caruso, Benjamin
[1]
;
Sanchez, Julieta M.
[1]
;
Garcia, Daniel A.
[1]
;
de Paula, Eneida
[2]
;
Perillo, Maria A.
[1]
Número total de Autores: 5
|
| Afiliação do(s) autor(es): | [1] Univ Nacl Cordoba, CONICET, IIBYT, Catedra Quim Biol, Dept Quim, FCEFyN, RA-5000 Cordoba - Argentina
[2] Univ Estadual Campinas, Inst Biol, Dept Bioquim, Campinas, SP - Brazil
Número total de Afiliações: 2
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Cell Biochemistry and Biophysics; v. 66, n. 3, p. 461-475, JUL 2013. |
| Citações Web of Science: | 2 |
| Resumo | |
Combined effects of flunitrazepam (FNZ) and lidocaine (LDC) were studied on the thermotropic equilibrium of dipalmitoyl phosphatidylcholine (dpPC) bilayers. This adds a thermodynamic dimension to previously reported geometric analysis in the erythrocyte model. LDC decreased the enthalpy and temperature for dpPC pre- and main-transitions (Delta H (p), Delta H (m), T (p), T (m)) and decreased the cooperativity of the main-transition (Delta T (1/2),(m)). FNZ decreased Delta H (m) and, at least up to 59 mu M, also decreased Delta H (p). In conjunction with LDC, FNZ induced a recovery of a dagger T (1/2,m) control values and increased Delta H (m) even above the control level. The deconvolution of the main-transition peak at high LDC concentrations revealed three components possibly represented by: a self-segregated fraction of pure dpPC, a dpPC-LDC mixture and a phase with a lipid structure of intermediate stability associated with LDC self-aggregation within the lipid phase. Some LDC effects on thermodynamic parameters were reverted at proper LDC/FNZ molar ratios, suggesting that FNZ restricts the maximal availability of the LDC partitioned into the lipid phase. Thus, beyond its complexity, the lipid-LDC mixture can be rationalized as an equilibrium of coexisting phases which gains homogeneity in the presence of FNZ. This work stresses the relevance of nonspecific drug-membrane binding on LDC-FNZ pharmacological interactions and would have pharmaceutical applications in liposomal multidrug-delivery. (AU) | |
| Processo FAPESP: | 06/00121-9 - Novas formulações de anestésicos locais de liberação controlada: do desenvolvimento ao teste clínico odontológico |
| Beneficiário: | Eneida de Paula |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |