Perfluorocarbon nanoemulsions can deliver lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or 19F MRI. In the first generation of block copolymer stabilized perfluorocarbon nanoemulsions, perfluoropentane (PFP) was used as the droplet forming compound. Although manifesting excellent therapeutic and ultrasound imaging properties, PFP nanoemulsions were unstable at storage, difficult to handle, and underwent hard to control phenomenon of irreversible droplet-to-bubble transition upon injection. To solve the above problems, perfluoro-15-crown-5-ether (PFCE) was used as a core forming compound in the second generation of block copolymer stabilized perfluorocarbon nanoemulsions. PFCE nanodroplets manifest both ultrasound and fluorine (19F) MR contrast properties, which allows using multimodal imaging and 19F MR spectroscopy for monitoring nanodroplet pharmacokinetics and biodistribution. In the present paper, acoustic, imaging, and therapeutic properties of unloaded and paclitaxel (PTX) loaded PFCE nanoemulsions are reported. As manifested by the 19F MR spectroscopy, PFCE nanodroplets are long circulating, with about 50% of the injected dose remaining in circulation two hours after the systemic injection. Sonication with 1-MHz therapeutic ultrasound triggered reversible droplet-to-bubble transition in PFCE nanoemulsions. Microbubbles formed by acoustic vaporization of nanodroplets underwent stable cavitation. The nanodroplet size (200 nm to 350 nm depending on a type of the shell and conditions of emulsification) as well as long residence in circulation favored their passive accumulation in tumor tissue that was confirmed by ultrasonography. In the breast and pancreatic cancer animal models, ultrasound-mediated therapy with paclitaxel-loaded PFCE nanoemulsions showed excellent therapeutic properties characterized by tumor regression and suppression of metastasis. Anticipated mechanisms of the observed effects are discussed.

To measure instantaneous velocity fields of venous blood flow in a rat using X-ray particle tracking method. Gold nanoparticles (AuNPs) incorporated chitosan microparticles were applied as biocompatible flow tracers. After intravenous injection of the AuNP-chitosan particles into 7- to 9-week-old male rat vein, X-ray images of particle movement inside the cranial vena cava were consecutively captured. Individual AuNP-chitosan particles in the venous blood flow were clearly observed, and the corresponding velocity vectors were successfully extracted. The measured velocity vectors are in good agreement with the theoretical velocity profile suggested by Casson. This is the first trial to measure blood flow in animals under in vivo conditions with X-ray imaging technique. The results show that X-ray particle tracking technique has a great potential for in vivo measurements of blood flow, which can extend to various biomedical applications related with the diagnosis of circulatory vascular diseases.

A developed assay method to evaluate the pharmacokinetics of phenytoin in human plasma was investigated by reverse-phase HPLC-UV. We found the analytic condition that separate phenytoin from internal standard (triamcinolone acetonide) in human plasma sample at the wavelength of 225 nm. Proteins of the plasma samples were removed enough by using 0.1 N HC1. Mobile phase is consisted of buffer (pH3.0):CH3CN (65:35), and retention time of phenytoin is 8.2 min at a flow rate of 0.9 ml/min.. Tlie fundamental parameters such as linearity, accuracy, precision for this bioanalytical method validation were suitable to pharmacokinetic study and bioequvalence test. Eight volunteers in lasting were administered single dose of 100 mg of phenytoin (one tablet) orally together with 240 ml water for pharmacokinetic studies. The maximum concentration (0.82 ㎍/ml) of phenytoin was attained at 6.63 hour after dosing. T1/2 and AUC were 14.88 hr and 25.181 ㎍hr/ml respectively. According to our study, the accurate analysis for phenytoin achieved and the proposed guidance can be applied to pharmacokinetic study and bioequivalence test in human.