griseofulvin and Hemolysis

To investigate the use of nano self-assemblies formed by polyallylamine (PAA) modified with 5 or 10% mole fluorenylmethoxy carbonyl (Fmoc(5)/(10)), dimethylamino-1-naphthalenesulfonyl (Dansyl(5)/(10)) and 5% mole cholesteryl group (Ch(5)) for oral hydrophobic drug delivery.. Propofol, griseofulvin and prednisolone were loaded into amphiphilic PAAs. Particle size and morphology of drug-loaded self-assemblies were determined using photon correlation spectroscopy and transmission electron microscopy. Solubilising capacity, in vitro drug release and formulation stability were analysed by HPLC, and in vitro biocompatibility studies (haemolysis and cytotoxicity) were carried out on bovine erythrocytes and Caco-2 cells, respectively. Dansyl(10) and Ch(5) griseofulvin formulations were administered intra-gastrically to rats, and drug plasma levels were analysed by HPLC.. Drug-encapsulated self-assemblies typically have hydrodynamic size of 300-400 nm. Dansyl(10) exhibited universal drug solubiliser property and had significantly improved prednisolone, griseofulvin and propofol solubility by 145, 557 and 224-fold, respectively. Fmoc polymers resulted in modest drug solubility improvement. These polymers were non-haemolytic, did not enhance cytotoxicity compared to unmodified PAA, and demonstrated significant increase in griseofulvin plasma concentration compared to griseofulvin in water after oral administration.. Ch(5) and Dansyl(10) showed promising potential as nano-carriers for oral hydrophobic drug delivery.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Caco-2 Cells; Cattle; Cell Survival; Cholestenes; Dansyl Compounds; Drug Carriers; Fluorenes; Griseofulvin; Hemolysis; Humans; Hydrophobic and Hydrophilic Interactions; Hypnotics and Sedatives; Male; Polyamines; Prednisolone; Propofol; Rats; Rats, Sprague-Dawley

Human red blood cells (RBCs) were lysed by in vitro irradiation in the presence of the antifungal drug griseofulvin (GF). Effects of UVA fluence and GF concentration on photohaemolysis were examined under aerobic conditions. The photohaemolysis occurred at much lower fluence than that necessary for oxidation of the membrane lipids. UVA-irradiated solution of GF did not cause haemolysis. The photohaemolysis was colloid osmotic in nature because it was preceded by K+ leakage from the cells and was delayed in the presence of 30 mM sucrose in the medium. Even under anaerobic conditions, RBCs were lysed by irradiation with higher fluence than that required for aerobic photohaemolysis. Therefore, some phototoxic mechanism other than photosensitized oxidation is also involved in the photohaemolysis.

Topics: Aerobiosis; Anaerobiosis; Dose-Response Relationship, Radiation; Erythrocytes; Griseofulvin; Hemolysis; Humans; Kinetics; Ultraviolet Rays