Thermal and 31P-NMR studies to elucidate sumatriptan succinate entrapment behavior in Phosphatidylcholine/Cholesterol liposomes. Comparative 31P-NMR analysis on negatively and positively-charged liposomes

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 105; pp. 14 - 23
• Main Authors: Villasmil-Sánchez, Sheila, Rabasco, Antonio M., González-Rodríguez, M. Luisa
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2013
• Subjects: 31PNMR spectrum; Amines - pharmacology; Calorimetry, Differential Scanning; cholesterol; Cholesterol - chemistry; Cholesterol - metabolism; colloids; Differential scanning calorimetry; drugs; encapsulation; Lipid Bilayers - metabolism; Liposomes; Liposomes - chemistry; Magnetic Resonance Spectroscopy; melting; microscopy; nuclear magnetic resonance spectroscopy; Organophosphates - pharmacology; phosphatidylcholines; Phosphatidylcholines - chemistry; Phosphatidylcholines - metabolism; Phospholipid membrane; phosphorus; Structural conformations; succinic acid; Sumatriptan - chemistry; Sumatriptan - metabolism; Sumatriptan succinate; Thermal analysis; Sumatriptan succinate; Differential scanning calorimetry; Structural conformations; Liposomes; Thermal analysis; Phospholipid membrane; 31PNMR spectrum
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2012.12.019

Cationic liposomes without a charge showed a 31P-NMR spectrum with phases coexistence. The sumatriptan succinate incorporation changes the 31P-NMR spectrum signals into a unique signal corresponding to liquid crystalline bilayer. This could mean stability in the liposomal membrane. [Display omitted] ► Chargeless liposomes are unable to encapsulate sumatriptan succinate. ► By DSC an interaction between Phosphatidylcholine and sumatriptan succinate was observed. ► Charged liposomes are suitable for encapsulation of sumatriptan succinate. ► Bilayer structure in a liquid crystalline phase of the positively-charged REV liposomes membrane showed a great stability. ► Different conformational structures caused lower entrapment values. In this paper, two techniques, differential scanning calorimetry (DSC) and phosphorus nuclear magnetic resonance (31P-NMR), have been used to characterize sumatriptan succinate-loaded charged liposomes. To complete the results obtained by DSC a hot stage microscopy (HSM) technique was used. Data concerning the drug entrapment efficiency were published in a previous paper. The differences in data concerning encapsulation into negatively and positively-charged vesicles, indicated an influence of drug in the structural conformation of lipids in the bilayer. Moreover, the inability to formulate chargeless vesicles contributed to the opinion that a physical formulation study might be relevant. Phosphatidylcholine and cholesterol were used as lipid film forming agents, whereas stearylamine (positive) and dicetylphosphate (negative) were added as charge-inducing agents. DSC studies demonstrated that phosphatidylcholine caused the disappearance of the melting peak (Tm) of sumatriptan succinate because a drug dissolution process occurs. In addition, thermograms showed interesting interactions between stearylamine and dicetylphosphate with sumatriptan succinate favoring drug entrapment into the liposomes. In the present work, 31P-NMR technique demonstrated that the structural conformation of lipids in the membrane affected drug encapsulation into multilamellar (MLVs) and unilamellar (LUVs) vesicles. Bilayer structure in a liquid crystalline phase of the positively-charged REV liposomes membrane has demonstrated a high structural stability and a better encapsulation efficacy for sumatriptan succinate than negatively-charged TLE and REV liposomes. Therefore, phosphatidylcholine interaction with sumatriptan succinate appears to be the cause of the inability to obtain neutral sumatriptan succinate liposomes.