Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1–20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.
Indirubin is an active component of Dang Gui Long Hui Wan, which has been used in traditional Chinese medicine to treat inflammatory diseases as well as for the prevention and treatment of human cancer, such as chronic myeloid leukemia. The therapeutic effects of indirubin analogs have been underestimated due to its poor water solubility and low bioavailability. To improve the solubility and bioavailability of indirubin analogs, we prepared a mixed micellar formulation with Kolliphor® EL and Tween 80 as surfactants, and PEG 400 as a co-surfactant, followed by complexation with (2-hydroxyproply)-β-cyclodextrin at appropriate ratios. Overall, improving the solubility and skin penetration of indirubin analogs can increase clinical efficacy and provide maximum flux through the skin.
Tracking loss due to zero mean measurement noise has recently been discovered in PI controlled systems with antiwindup. This phenomenon was referred to as "Noise-Induced Tracking Error (NITE)" and the error was quantified for a particular type of anti-windup in previous work. In this paper, we give analyses of NITE with general types of anti-windup. Specifically, several anti-windup structures introduced in representative work are considered with PI controlled systems, and NITE for all systems are quantified in terms of system parameters and noise characteristics.
The effect of residual metallic sodium on the solidification cracking susceptibility of type 316FR stainless steel was investigated via transverse-Varestraint tests. And a solidification brittle temperature range (BTR) of type 316FR stainless steel was 37 K. However, the BTR expanded from 37 to 67 K, as the amount of metallic sodium at the specimen surface increased from 0 to 7.99 mg/cm 2. Microstructural observation of the weld metal suggested that metallic sodium existed in the weld metal, including in the cell boundaries, during welding solidification. Thermodynamic calculations suggested that sodium expanded the temperature range of solidliquid coexistence during welding solidification of the steel weld metal. Therefore, the increased solidification cracking susceptibility (i.e., expansion of the BTR) in the residual sodium environment was attributed to enhanced segregation of sodium during the welding solidification; this segregation, in turn, resulted in an expanded temperature range of solid-liquid coexistence.
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