Ding Li,Menglong Wang,Wen-Liang Song,Deng-Guang Yu,Sim Wan Annie Bligh
A side-by-side electrospinning process characterized by a home-made eccentric spinneret was established to produce the Janus beads-on-a-string products. In this study, ketoprofen (KET) and methylene blue (MB) were used as model drugs, which loaded in Janus beads-on-a-string products, in which polyvinylpyrrolidone K90 (PVP K90) and ethyl cellulose (EC) were exploited as the polymer matrices. From SEM images, distinct nanofibers and microparticles in the Janus beads-on-a-string structures could be observed clearly. X-ray diffraction demonstrated that all crystalline drugs loaded in Janus beads-on-a-string products were transferred into the amorphous state. ATR-FTIR revealed that the components of prepared Janus nanostructures were compatibility. In vitro dissolution tests showed that Janus beads-on-a-string products could provide typical double drugs controlled-release profiles, which provided a faster immediate release of MB and a slower sustained release of KET than the electrospun Janus nanofibers. Drug releases from the Janus beads-on-a-string products were controlled through a combination of erosion mechanism (linear MB-PVP sides) and a typical Fickian diffusion mechanism (bead KET-EC sides). This work developed a brand-new approach for the preparation of the Janus beads-on-a-string nanostructures using side-by-side electrospinning, and also provided a fresh idea for double drugs controlled release and the potential combined therapy.Keywords:side-by-side electrospinning;Janus structure;beads-on-a-string;immediate release;sustained release
Low-energy ultrasound (LEUS), exhibiting obvious advantages as a safe therapeutic strategy, would be promising for cancer therapy. We had synthesized a LEUS-responsive targeted drug delivery system based on functional mesoporous silica nanoparticle for cancer therapy. Paclitaxel (PTX) was loaded in mesoporous silica nanoparticles with a hydrophobic internal channel, and folic acid (FA) functionalized β-Cyclodextrin (β-CD) was capped on the surface of the nanoparticles (DESN), which acted as a cancer-targeting moiety and solubilizer. The existence of a hydrophobic internal channel in the DESN was beneficial to the storage of hydrophobic PTX, along with the enhancement of the cavitation effect produced by mild low-energy ultrasound (LEUS, ≤1.0 W/cm2, 1 MHz). The DESN showed significantly enhanced cavitation effect, selective targeting, and achieved a rapid drug release under mild LEUS. To investigate the in vivo antitumor efficacy of the DESN upon LEUS irradiation, we established a 4T1 mammary tumor model. The DESN were confirmed to be of great biodegradability/biocompatibility. The tumor growth was significantly inhibited when the mice were treated with DESN (10 mg/kg) + LEUS with the relative tumor volume reduced to 4.72 ± 0.70 compared with the control group (V/V0= 17.12 ± 2.75). The DESN with LEUS represented excellent inhibiting effect on tumor cell in vivo. This work demonstrated that DESN mediating dual mode chemo-sonodynamic therapy could be triggered by extracorporeal remote control, may suggest a promising clinical application in cancer therapy.Keywords:low-energy ultrasound;mesoporous silica;folic acid;rapid release;chemo-sonodynamic therapy