Study of aqueous phase aggregation of FTY720 (fingolimod hydrochloride) and its effect on DMPC liposomes using fluorescent molecular probes

Abstract

This work focuses on the study of aqueous phase aggregation of the recently FDA approved oral drug molecule FTY720 (fingolimod hydrochloride) and its effect on dimyristoylphosphatidylcholine (DMPC) liposomes using different fluorescent molecular probes and fluorescence parameters. The variation of the steady state fluorescence intensity of 8-anilino-1-naphthalene sulfonic acid (ANS) with FTY720 in water shows an efficient micellar aggregation with the critical micellar concentration (CMC) at ~75 μM. The aggregation number calculation from steady state fluorescence quenching of pyrene shows the formation of small micellar aggregates in aqueous solution having an aggregation number of 42 ± 3 with the free energy of micellization ~-23 kJ mol(-1). Fluorescence intensity and lifetime decay analysis of the molecular probe 1-naphthol indicate that the interaction of FTY720 with the DMPC lipid bilayer membrane prevents partitioning of small molecules such as 1-naphthol to the membrane in both solid gel (SG) and liquid crystalline (LC) phases. Temperature dependent fluorescence intensity studies of 1-naphthol and fluorescence anisotropy measurements of 1,6-diphenyl-1,3,5-hexatriene (DPH) have shown that above the CMC of FTY720, the SG to LC main phase transition temperature (T(M)) of the lipid bilayer membrane decreases from 23 °C to 21 °C in the aqueous medium.

Impact of bacterial endotoxin on the structure of DMPC membranes

“…1a) as a model for a biological membrane [16,17]. The molecular structure and dynamics of the bilayer is observed via solid state NMR on artificially introduced 2 H nuclei [18,19].…”

Effect of a glucose-triazole-hydrogenated cardanol conjugate on lipid bilayer membrane organization and thermotropic phase transition

“…3). The lowering of T m is a result of changes in acyl chain packing of lipid bilayer membrane [15][16][17]. At higher mol% (>7 mol%), the vanishing of T m in fluorescence anisotropy plot (Fig.…”

“…Such interactions result in significant changes in the structure and dynamics of lipid bilayer membranes [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Solubilisation and perturbation of lipid bilayer membranes using synthetic and biocompatible amphiphilic compounds has been used for isolation and purification of different membrane components [1][2][3][4][5][6][7][8][9][10][11][12][13][14].…”

“…Solubilisation and perturbation of lipid bilayer membranes using synthetic and biocompatible amphiphilic compounds has been used for isolation and purification of different membrane components [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. It is well known that the bioactivity and mechanistic properties of these amphiphilic compounds strongly depend on the nature of hydrophilic and hydrophobic groups [3][4][5][6][7][8][9][10][11][12][13][14]17] solubilisation of lipid bilayer membrane and thermotropic phase behaviour generally depends upon the molecular properties and concentration of the employed compound [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17].…”

New building blocks for convenient access to positional isomers of FTY720 and analogues

“…Also FTY720 was found to prevent the partitioning of small molecules like 1-naphthol into the lipid bilayer membrane. [11][12] With these results in hand, a need to study the effect of other positional isomers 2 and 3 of FTY720 on the lipid bilayer membrane became interesting and relevant. In this context there was a genuine need for a good synthetic scheme enabling access to these positional isomers of FTY720.…”