Kun Wei

Dual docetaxel/superparamagnetic iron oxide loaded nanoparticles for both targeting magnetic resonance imaging and cancer therapy.

Theragnostics polymer nanoparticles (NPs) loaded simultaneously with anticancer drug docetaxel (Dtxl) and superparamagnetic iron oxide (SPIO) nanocrystals were developed for both cancer therapy and ultrasensitive MRI. These multifunctional polymer vesicles were formed by carboxy-terminated poly(lactic-co-glycolic) acid using a single emulsion evaporation method. The active tumor-targeting single chain prostate stem cell antigen antibodies (scAb(PSCA)) were conjugated on the surface of polymer vesicles by using functional poly(ethylene glycol). The diameter of NPs was about 147 nm and the SPIO and drug encapsulation efficacy was 23% and 6.02%, respectively. Vibration simple magnetometer and X-ray diffraction proved that the superparamagnetic behavior of SPIO was not changed during NPs formation and modification. The NPs exhibited a triphasic drug release pattern in vitro over 30 days. Enhanced cellular uptake ability and antiproliferative effect of the targeted NPs in prostate cancer PC3 cell line by using the confocal laser scanning microscopy and cytotoxicity assay were observed. Moreover, the Prussian blue staining and the MRI assay in vitro demonstrated that the NPs have a high SPIO clustering effect. Therefore, these stable and tumor-targeting polymer NPs could be promising multifunctional vesicles for simultaneous targeting imaging, drug delivery and real time monitoring of therapeutic effect.

Investigations on the formation mechanism of hydroxyapatite synthesized by the solvothermal method

In this paper, uniform hydroxyapatite (HA) nanowires of width 60 nm and length 1 µ ma re synthesized by solvothermal synthesis. The formation process of the nanowires has been elaborated from the structure within the reverse micelles b yt hetime-resolved fluorescence quenching technique. The results reveal that the formation of amorphous nuclear/surfactant complex and the electrostatic field within the reverse micelles maintain the unidirectional, irreversible fusion of reverse micelles, leading to the growth of nanowires in one direction. In the solvothermal synthesis, the pressure generated in the autoclave is estimated. The results suggest that the products are prepared under stable conditions without intense shearing stress where it is favourable for the formation of long and uniform HA nanowires.

Synthesis, characterization and osteoconductivity properties of bone fillers based on alendronate-loaded poly(ε-caprolactone)/hydroxyapatite microspheres

A superior drug controlled release system capable of achieving efficient osteogenesis is in imperative demand because of limited bone substitute tissue for the treatment of bone defect. In the present study, we investigated the potential of using poly(ε-caprolactone)–hydroxyapatite (PCL–HA) composite microspheres as an injectable bone repair vehicle by controlled release of alendronate (AL), a medicine that belongs to the bisphosphonates family. The PCL/HA–AL microspheres were prepared with solid/oil/water emulsion technique, which included two processes: (1) AL was loaded on the hydroxyapatite nanoparticles; (2) the HA–AL complex was built in the PCL matrix. The spherical PCL/HA–AL microspheres were characterized with its significantly improved encapsulation efficiency of hydrophilic AL and better sustained release. Human bone mesenchymal stem cells (hMSCs) were cultured on the surface of these microspheres and exhibited high proliferative profile. Specifically, in osteogenic medium, hMSCs on the surface of PCL/HA–AL microspheres displayed superior osteogenic differentiation which was verified by alkaline phosphatase activity assay. In conclusion, by presenting strong osteogenic commitment of hMSCs in vitro, the PCL/HA–AL microspheres have the potential to be used as an injectable vehicle for local therapy of bone defect.

Solvothermal Synthesis of Calcium Phosphate Nanowires Under Different pH Conditions

Nano‐size calcium phosphate is prepared via solvothermal synthesis methods, using a reverse micelles solution. The influence of pH value on the crystallinity, morphology, and composition of the nanoparticles are investigated. It was found that the crystallinity increased as pH increased. However, notable changes in the morphology of the final products can be observed. At pH 6.0, long nanowires (800 nm long and 30∼100 nm wide) are observed. For pH=7.5, the nanowires are straight with 60 nm diameter and a length>1500 nm. The materials prepared at pH=8.5 exhibit short‐rod morphologies with a dimension of 130∼160 nm in length and 20∼30 nm in width. As for those prepared at pH=9.5, short rods 80∼100 nm in length and 20∼50 nm in width can be observed. The influence of pH value on the interaction between surfactant molecules and reactant ions are responsible for these differences. In addition, the composition of the finial precipitation also depends on pH. Meanwhile, the ability to generate high axial ratio and well‐crystallized nanowires, by coorganization of reverse micelles solutions and hydrothermal synthesis techniques, as described in this work, could offer an approach to the fabrication of one dimension nanomaterials.

Enhancement of compressive strength and cytocompatibility using apatite coated hexagonal mesoporous silica/poly(lactic acid-glycolic acid) microsphere scaffolds for bone tissue engineering

In this study, hexagonal mesoporous silica (HMS) was composited with poly(lactic acid-glycolic acid) (PLGA) to enhance the compressive strength of pure PLGA microsphere scaffolds. The compressive strength of the HMS/PLGA composite scaffolds was significantly higher than that of pure PLGA scaffolds, which was more suitable for bone repair. However, the proliferation of mouse mesenchymal stem cells (MSCs) cultured on HMS/PLGA was inhibited when the HMS content was high. To promote the cytocompatibility of HMS/PLGA scaffolds, apatite were deposited on the scaffolds surface by an in vitro biomineralization process. After biomineralization, the cytocompatibility of mineralized scaffolds was significantly improved and without cytotoxicity. And the compressive strength of the mineralized scaffolds was close to that of the original scaffolds. Considering the suitable compressive strength and good cytocompatibility, the mineralized HMS/PLGA microsphere scaffolds would open a new door to major bone tissue engineering.

Insight into Shape Control Mechanism of Calcium Phosphate Nanoparticles in Reverse Micelles Solution

The present experiment demonstrates a systematic morphosynthesis of calcium phosphate crystals with controlled morphology in reverse micelles solution of CTAB/n‐pentanol/water/cyclohexane. Well‐defined morphologies of calcium phosphate particles, such as nanowires, tablets, brushlike particles, and fiber bundles, can be prepared. The microstructural characteristics of the CTAB/n‐pentanol/water/cyclohexane reverse micelles solution has been investigated by FTIR spectroscopic, 31P NMR, and UV‐visible absorption spectra techniques, demonstrating that the molar ratio of water to surfactant (W o ) and n‐pentanol to surfactant (P o ) showed significant effects on the morphology of the resulting particles. At lower W o and P o , CTAB played a role in guiding the growth direction. With increasing W o and P o , crystal growth lost the direction‐guiding capability of CTAB. However, as crystal growth modifiers, water and cosurfactants follow different mechanisms. The solubility of water causes a decrease in bound water layer, resulting in a decrease in interactions between CTA+ and PO4 3− which invalidates the shape control of surfactant molecules. The loading of cosurfactant (n‐pentanol) results in decreasing the rigidity of the reverse micelles interface. This in turn favors the shape fluctuations of reverse micelles, inducing crystal development.

A mesoporous silicon/poly-(DL-lactic-co-glycolic) acid microsphere for long time anti-tuberculosis drug delivery.

In this study, drug delivery systems for controlling release of hydrophobic anti-tuberculosis (TB) drug-rifampicin (RIF) or hydrophilic anti-TB drug-isoniazid (INH) from mesoporous silica (MS) were fabricated. The drug was first filled into the mesopores of MS particles, and then the drug-laden MS constructs were incorporated into the bulk of poly-(DL-lactic-co-glycolic) acid (PLGA) microspheres. In comparison with mono-component construct (drug-laden MS and drug-laden PLGA), this multi-component system significantly improved the release time of RIF and INH. For drug-laden MS, about 100% INH was released after 15 h, and about 70% RIF was released after 50 h. For drug-laden PLGA, about 100% INH and RIF were released after 30 and 40 days, respectively. After 60 days, the total RIF and INH release from MS/PLGA had only reached around only 48% and 57%, respectively. This MS/PLGA system could significantly prolong RIF or INH release compared to MS and PLGA. CCK-8 assay demonstrated that this MS/PLGA system had no cytotoxicity. And there has not been study of documenting the controlled release of anti-TB drugs such as RIF or INH from MS/PLGA. Considering the long time release of RIF and INH from MS/PLGA, a new door to bone TB would be opened.

Kinetic Studies on the Synthesis of Hydroxyapatite Nanowires by Solvothermal Methods

Hydroxyapatite nanowires with a high axial ratio have been synthesized in reverse micelle solutions that consist of cetyltrimethylammonium bromide (CTAB), n-pentanol, cyclohexane, and the reactant solution by solvothermal methods. This paper focusses on the kinetic studies of the solvothermal reaction and the linear growth of hydroxyapatite nanowires. When the reaction was carried out at low temperatures (65°C), the experimental results showed that the reaction rate was of zero order since the whole reaction was diffusion controlled with constant diffusion coefficients. In the middle to high temperature range (130–200°C), the kinetics were characterized by second order reaction kinetics. Since the controlling factor was activation energy and the apparent activation energy was large, the reaction rate was more sensitive to the temperature. Therefore, the exponent of the reaction rate constant increased by two when the temperature was increased from 130 to 200°C. By calculating the yields of products and the specific surface areas at different times, the linear and overall growth rate equations of the hydroxyapatite nanowires could be obtained. The experimental effective growth order of the crystals was 11. The larger growth order indicated that the crystal could grow more effectively in one direction because of the induction of the surfactant in the experiment system.

Preparation of Bioactive Nanoparticles in the System CaO-P2O5-SiO2 Using Microemulsions

The bioactive nanoparticles in the system CaO-P2O5-SiO2 were synthesized via microemulsions method in this study. The structure and properties of the nanoparticles were investigated in details using XRD, TEM, FTIR, BET techniques. It was found that, in a stable phase W/O emulsions, the diameter of the nanoparticles were related to the molar ratio of water to surfactant (γ). Under the favorable conditions, i.e. γ=6, nano-sized spherical amorphous particles could be obtained with the average diameter of 25 nm. The microemulsions could be an alternative method to prepare bioactive nanoparticles for bone reparation and bone tissue engineering scaffolds.

Preparation of Hydroxyapatite/Poly(ε-caprolactone) Hybrid Microspheres for Drug Release System

Hydroxyapatite(HA) nanoparticles with hydrophobic surface have been synthesized using mono-alkyl phosphate (MAP) as modifier by hydrothermal synthesis method. The drug-loaded nano-HA/ Poly(ε-caprolactone)（PCL）composite microspheres and drug-load PCL microspheres were fabricated by an S/O/W emulsion solvent evaporation method. The microspheres morphology was investigated by scanning electron microscopy (SEM). Drug distribution in microsphere matrix was studied by confocal laser scanning microscope (CLSM). The results showed that the drug distributed evenly in the drug-HA-PCL microspheres, but only around the surface of the drug-PCL microspheres. The drug release profile showed that the nano-HA/PCL hybrid microspheres had low initial burst and could release continually for 90 days. This kind of hybrid microspheres can be used as a promising long-term drug delivery system in the bone.