RESUMEN
The effect of novel 3-{4-[2-hydroxyl-(1-methyl ethylamine) propyl oxygen]phenyl}propionic acid cetylester (PAC) as a surface modification ligand on the delivery of liposomes into cultured cardiomyocytes was investigated. Small unilamellar liposomes with and without PAC (PAC-liposome and Plain-liposome) were labeled with a fluorescence marker. The cultured neonatal cardiomyocytes were incubated with liposomes under normoxia or hypoxia conditions, and then the cell-associated fluorescence was measured. A high affinity of the PAC-liposomes to cardiomyocytes was observed. The amount of cell uptake of PAC-liposomes under normoxia conditions was 4-fold higher than that of plain-liposome, and the increase was 8.5-fold when hypoxia occured. The results suggested that PAC is a potential surface modification ligand for liposome targeting the ischemic myocardium.
Asunto(s)
Sistemas de Liberación de Medicamentos , Liposomas , Miocitos Cardíacos/efectos de los fármacos , Animales , Animales Recién Nacidos , Células Cultivadas , Portadores de Fármacos , Ligandos , Isquemia Miocárdica/tratamiento farmacológico , Ratas , Ratas Wistar , Propiedades de SuperficieRESUMEN
This report firstly describes the pharmacokinetic study of liposomal breviscapine (LB) after oral administration in rats. The mean Cmax and AUC(0-->t) of LB were 3.3 and 3.1-fold higher than those of breviscapine solution (BS). The oral absorption of breviscapine was significantly increased after encapsulation in the liposomal formulation.
Asunto(s)
Anticoagulantes/farmacocinética , Flavonoides/farmacocinética , Animales , Anticoagulantes/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Portadores de Fármacos , Composición de Medicamentos , Femenino , Flavonoides/administración & dosificación , Liposomas , Masculino , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Espectrofotometría UltravioletaRESUMEN
Small unilamellar liposomes (SUV) of different phospholipid/polymer composition were labeled with NBD-PC, which served as a bilayersituated fluorescence marker. Neonatal cardiomyocytes were incubated with liposomes and then the cell-associated fluorescence was measured. The factors influencing the liposome uptake by cardiomyocytes such as concentration of lipid, time of incubation, membrane fluidity of liposomes, charge lipid/polymer modification of liposomes and anoxia of cultured cardiomyocytes were investigated. The liposome uptake by cardiomyocytes increased dose-dependently and time-dependently. Liposome uptake was strongly influenced by the electrical charge and modified polymer. After 2 h incubation, the uptake of positively charged liposomes was 1.7-fold higher than that of negatively charged one and both higher than that of the neutral one. The presence of PE-PEG2000 distinctly reduced the liposome uptake and the difference between the uptake of charged and neutral liposome. Anoxia increased the uptake of liposome at the first hour (increased 20%), but after 2 h incubation the liposome uptake by hypoxia cellswas less than that of normoxia cells (decreased 18%). Mechanisms involved are also discussed.