simple and sensitive HPLC method for fluorescence quantitation of doxorubicin in micro-volume plasma: applications to pharmacokinetic studies in rats

A validated HPLC method was developed to determine the doxorubicin concentration in a small volume of rat plasma [60 microL] with convenient fluorescence detection. Sample preparation includes a simple one-step liquid-liquid extraction using a minimum amount of organic solvent, with extraction recovery more than 95%. The analysis was accomplished using PerfectSil C18 column maintained at 35 [degree]C and a mobile phase consisted of acetonitrile and water [32:68, v/v; pH=2.6]. The flow-rate was kept at 1 mL/min and the column effluent was monitored with a fluorescence detector at an excitation and emission wavelength of 470 and 555 nm, respectively. The detection limit was 5 ng/mL. No analytical interference was observed from endogenous components in the rat plasma. This method was feasibly applied to the pharmacokinetic study of 5 mg/Kg of doxorubicin after the intravenous administration to rats

Preparation and characterization of stable Nanoliposomal formulation of fluoxetine as a potential adjuvant therapy for drug-resistant tumors

Chemotherapy research highly prioritizes overcoming the multidrug resistance [MDR] in human tumors. Liposomal formulation of fluoxetine, as a fourth generation chemosensitizer, was constructed and characterized for percent entrapment, release profile, morphology, particle size, zeta potential and stability. Liposomes were prepared using different active loading techniques. The influence of different formulation variables such as loading methodology, type of main lipid, addition of PEGylated lipid and cholesterol percentage was evaluated to achieve required entrapment efficiency, in vitro release behavior and stability. The studied parameters had significant effect on physicochemical characteristics of the nanocarriers. High fluoxetine encapsulation efficiency [83% +/- 3%] and appropriate particle size [101 +/- 12 nm] and zeta potential [-9 +/- 2 mv] were achieved for PEGylation liposomes composed of DSPE-PEG, DSPC and cholesterol at respective molar ratio of 5:70:25. An in vitro fluoxetine release of about 20% in 48 h was observed from optimum formulation. Atomic force microscopy [AFM] studies confirmed homogeneous distribution of particles and spherical shape with smooth surface. The optimum formulation was stable for 9 days when incubated at 37 [degree sign]C. The results of this study are very encouraging for application of the developed fluoxetine liposomal formulation in drug-resistant tumor models

Synthesis of N-arylmethyl substituted indole derivatives as new antiplatelet aggregation agents

A number of N-arylmethyl substituted indole derivatives have been synthesized and their effectiveness against ADP and arachidonic acid induced platelet aggregation in human plasma was determined. The desired compounds were synthesized by reacting the appropriate aniline derivative with isatin [or substituted isatin] to form the corresponding imine structures. The so formed compound was then activated using sodium hydride and reacted with the proper substituted benzyl halides. Among the tested compounds, derivatives 4a, 4c, 4d, 4f-i and 4k were the most potent compounds with satisfactory IC[50] values [under 38.5 micro M] for inhibition of platelet aggregation induced by arachidonic acid. All indole derivatives without substitution on position 1 of the indole ring, exhibited either weaker activities or were not active at all