Pharmacokinetic and tissue distribution of paclitaxel in rabbits assayed by LC‐UV after intravenous administration of its novel liposomal formulation

Abstract

A simple, rapid and sensitive LC-UV method was developed and validated for the determination of paclitaxel (PTX) in rabbit plasma and tissues. A 2 mL aliquot of acetonitrile and 10 μL ammonium acetate (pH 5.0, 6 m) as extraction agents were used to markedly increase the extraction recoveries and greatly reduce the endogenous substances. The separation was achieved on a C18 column at 30 °C using an acetonitrile-ammonium acetate buffer (pH 5.0, 0.02 m; 55:45, v/v) at a flow rate of 1.0 mL/min; UV detection was used at 227 nm. Good linearity was obtained between 0.025 and 10,000 µg/mL for plasma and between 0.025-200,000 µg/g for tissue samples (r > 0.999). The limit of detection was 6 ng/mL in plasma, 8 ng/g in heart and 12.5 ng/g in other tissues. The limit of quantitation was 25 ng/mL in plasma and heart, 125 ng/g in other tissues. The intra- and inter-day assays of precision and accuracy for all bio-samples ranged from 1.38 to 9.60% and from 83.6 to 114.5%, respectively. The extraction recoveries ranged from 70.1 to 109.5%. Samples were stable during three freeze-thaw cycles or stored in a freezer at -20 °C for 30 days. The assay method was successfully applied to a study of the pharmacokinetics and tissue distribution of novel PTX lung targeting liposomes.

Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes

“…[22][23][24][25][26][27][28] Furthermore, the liposomes can improve the oral bioavailability of drugs poorly absorbed through the gastrointestinal tract and alter the in vivo distribution of the drugs encapsulated into liposomes, to increase the therapeutic index. 22,[29][30][31][32] Currently, liposomes have been considered one of the most promising drug delivery carriers.…”

“…6 However, due to its low hydrophilicity and poor absorption following oral administration, the low oral bioavailability of BA limits its therapeutic efficacy and clinical application. 13,16 Therefore, on the basis of our previous studies, 23,24 the novel effervescent dispersion technique was used to develop BA-LP for the first time.…”

“…23,24 Briefly, BA (96 mg), HSPC (96 mg), Tween 80 (50 mg), and citric acid (50 mg) were dissolved in 5 mL of ethanol. The solution was filtered through a 0.22 µm hydrophobic membrane and then added into 10 mL of NaHCO 3 water solution (0.35%, w/v) at 5°C-8°C while the system was stirred, using a half-moon paddle stirrer at 1,000 rpm, for about 1 hour.…”

“…It has been demonstrated that liposomes can increase drug solubility and stability as well as provide good drug loading for both hydrophilic and lipophilic drugs. [22][23][24][25][26][27][28] Thus, a number of studies showed the liposome carrier could improve the oral bioavailability of poorly bioavailable drugs and change the in vivo distribution of entrapped drugs. [29][30][31][32] For example, Wang et al developed long-circulating nanoliposomes of quercetin, prepared by the emulsified evaporation-low temperature solidification method, using glyceryl behenate and Tween ® 80 as carriers.…”

Pharmacokinetics of quercetin-loaded nanodroplets with ultrasound activation and their use for bioimaging

“…This finding can be attributed to the protection provided by the lipid membranes and slow drug release from the formulation. 59 A previous in vitro report by Paliwal et al indicated that pretreatment of cells with ultrasound may change the concentration of quercetin in treated cell lines. 27 Our in vivo experiment demonstrated that the C 5 min increased from 0.5±0.1 μg/mL to 0.9±0.2 μg/mL after treatment with ultrasound (Table 2).…”