Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy.

A mixture of docetaxel (DTX) and Solutol(®) HS 15 (Solutol) transiently formed nanodroplets when it was suspended in an aqueous medium. However, nanodroplets that comprised DTX and Solutol showed a rapid precipitation of DTX because of their unstable characteristics in the aqueous medium. The incorporation of nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent stabilization was designed to prepare multilayer nanoparticles (NPs) with a DTX-loaded Solutol nanodroplet (as template NPs) core for an efficient delivery of DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets (~11.7 nm) were observed to have an increased average diameter (from 11.7 nm to 156.1 nm) and a good stability of the hydrated NPs without precipitation of DTX by vesicle fusion and multilayered structure, respectively. Also, a long circulation of the multilayer NPs was observed, and this was due to the presence of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved antitumor efficacy based on the enhanced permeation and retention effect. Therefore, this study indicated that the multilayer NPs have a considerable potential as a drug delivery system with an enhanced therapeutic efficacy by blood circulation and with low side effects.

Sol-gel transition of nanoparticles/polymer mixtures for sustained delivery of exenatide to treat type 2 diabetes mellitus.

The sol-gel transition of nanoparticles (NPs)/polymer mixture in aqueous medium was investigated for the sustained delivery of exenatide to treat type 2 diabetes mellitus. Exenatide-loaded multilayer NPs were prepared using a layer-by-layer approach which utilized the interaction between Pluronics and lipid bilayers as the main driving force for the construction of the multilayer. Pluronic F-127 was the polymer used, and it forms a gel at body temperature. Although the antidiabetic effects of exenatide-loaded multilayer NPs have been demonstrated previously in an animal model, in this work, the attempt was made to demonstrate the extended duration of antidiabetic effects, which was accomplished by localizing the exenatide-loaded NPs in muscular areas in the body through the gelation of Pluronic F-127. Transmittance electron microscopy and dynamic light scattering were used to examine the morphology of the multilayer NPs/polymer mixture. A change in the release pattern of exenatide was observed after gel formation at body temperature, and Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis was performed using native exenatide and a reference biomarker as control to observe whether exenatide extracted from the multilayer NPs and the multilayer NPs/Pluronic F-127 mixture degraded or not. We then observed the antidiabetic effect of exenatide-loaded multilayer NPs/Pluronic F-127 mixture by monitoring blood-glucose levels in db/db mice. In vitro and in vivo correlation was discussed regarding structural variation in the delivery vehicles.

Effect of HIFU treatment on tumor targeting efficacy of docetaxel-loaded Pluronic nanoparticles.

Numerous studies have been performed to identify the microenvironment of solid tumors, which is responsible for the insufficient delivery of anticancer drugs to tumor cells due to the poorly organized vasculature and the increased interstitial fluid pressure. As a result, the extravasation of convection-dependent agents including NPs is severely limited. Therefore, we have demonstrated the feasibility of targeting an enhancement of docetaxel-loaded Pluronic nanoparticles (NPs) using high-intensity focused ultrasound (HIFU) as an external stimulus-induced clinical system in tumor tissue. The efficient extravasation of NPs into the interior cells in tumor tissue was induced by relatively low HIFU exposure without apparent acute tissue damage. The enhanced targeting of NPs with near-infrared fluorescence dye was observed in tumor-bearing mice with various HIFU exposures. As a result, the greatest accumulation of NPs at the tumor tissue was observed at an HIFU exposure of 20 W/cm(2). However, the tumor tissue above at 20 W/cm(2) appeared to be destroyed and the tumor targetability of NPs was significantly decreased owing to thermal ablation with necrosis, resulting in the destruction of the tumor tissue and the blood vessels. In particular, a cross-sectional view of the tumor tissue verified that the NPs migrated into the middle of the tumor tissue upon HIFU exposure. The preliminary results here demonstrate that HIFU exposure through non-thermal mechanisms can aid with the extravasation of NPs into the interior cells of tumors and increase the therapeutic effect in enhanced and targeted cancer therapy.