Jie-Xin Wang

Preparation and characterization of porous hollow silica nanoparticles for drug delivery application.

Porous hollow silica nanoparticles (PHSNP) with a diameter of 60-70 nm and wall thickness of approximately 10nm were synthesized by using CaCO(3) nano-particles as the inorganic template. The characterization of PHSNP by TEM and BET indicated that PHSNP were uniform spherical particles with good dispersion, and had a specific surface area of 867 m(2)/g. The as-synthesized PHSNP were subsequently employed as drug carrier to investigate in vitro release behavior of cefradine in simulated body fluid. UV-spectrometry and TG analyses were performed to determine the amount of cefradine entrapped in the carrier. The BJH pore size distribution of PHSNP before and after entrapping cefradine was examined. Cefradine release profile from PHSNP followed a three-stage pattern and exhibited a delayed release effect.

Micronization of atorvastatin calcium by antisolvent precipitation process

Amorphous atorvastatin calcium (AC) ultrafine powder has been successfully prepared by antisolvent precipitation and spray drying process, in which hydroxypropyl methylcellulose (HPMC) was employed to control the particle size and morphology. The effects of experimental parameters, such as stirring time, drug concentration and drying methods, on particle size and morphology were investigated. The average particle size of AC obviously increased from 410 nm to 1200 nm as the stirring time changed from 30s to 60 min. The enhancement of drug concentration favored to decrease the particle size from 410 nm to 240 nm. After spray drying process, ultrafine AC powder was obtained, which had good dispersibility and narrow particle size distribution of 1-3 microm. The as-prepared ultrafine AC was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, thermal gravimetric analysis (TG), differential scanning calorimetry (DSC), specific surface area and dissolution test. The XRD analyses indicated that the ultrafine AC was amorphous. In the dissolution tests, the amorphous AC ultrafine powder exhibited enhanced dissolution property when compared to the raw material.

LyP-1 Modification To Enhance Delivery of Artemisinin or Fluorescent Probe Loaded Polymeric Micelles to Highly Metastatic Tumor and Its Lymphatics

Metastatic cancers are prone to form metastasis at a distance and acquire drug resistance, which are very common clinically and major obstacles to successful chemotherapy. Besides the tumor itself, the lymphatic system is increasingly emerging as a new target for anticancer therapy because it is an important route of tumor metastasis. To specifically deliver drug to both highly metastatic tumor and its lymphatics, tumor- and tumor lymphatics-homing peptide (LyP-1) conjugated PEG-PCL micelles (LyP-1-PM) were first constructed. Artemisinin (ART), a natural product with potential anticancer and antilymphangiogenesis effects, was chosen as the model drug and associated into the micelles. Both PM and LyP-1-PM had similar physiochemical properties, about 30 nm in size with uniform distribution. Highly metastatic breast cancer MDA-MB-435S cells and lymphatic endothelial cells (LEC) were applied as cell models. Flow cytometry and confocal microscopy studies showed that LyP-1-PM exhibited its specificity to both cell lines evidenced by its higher cellular uptake than PM. LyP-1-PM-ART demonstrated higher inhibition effect than PM-ART against these two cell lines in cell apoptosis, cell cycle and cytotoxicity tests. Near-infrared imaging showed that LyP-1-PM was distributed more in orthotopic MDA-MB-435S tumor than PM. Further study by colocalization indicated that PM accumulated near blood vessels, while LyP-1-PM further homed to tumor lymphatic vessels. LyP-1-PM achieved higher antitumor efficacy than other ART formulations in vivo with low toxicity. Both in vitro and in vivo studies here proved that LyP-1 modification enhanced the specific delivery of ART or fluorescent probe loaded polymeric micelles to MDA-MB-435S and LEC. Therefore, LyP-1-PM might be promising in terms of specific delivery of therapeutic or imaging agents to both highly metastatic breast tumor and its lymphatics.

Facile Preparation of Danazol Nanoparticles by High-Gravity Anti-solvent Precipitation (HGAP) Method

The nanoparticles of the hydrophobic drug of danazol with narrow size distribution are facilely prepared by controlled high-gravity anti-solvent precipitation (HGAP) process. Intensified micromixing and uniform nucleation environment are created by the high-gravity equipment (rotating packed bed) in carrying out the anti-solvent precipitation process to produce nanoparticles. The average particle size decreases from 55μm of the raw danazol to190nm of the nanoparticles. The Brunauer-Emmett-Teller (BET) surface area sharply increases from 0.66m^2•g^(-1) to 15.08 m^2g^(-1). Accordingly， the dissolution rate is greatly improved. The molecular state, chemical composition, and crystal form of the danazol nanoparticles remains unchanged after processing according to Fourier transform infrared (FTIR) and X-ray diffraction (XRD). The high recovery ratio and continuous production capacity are highly appreciated in industry. Therefore, the HOAP method might offer a general and facile platforrI1 for mass production of hydrophobic pharmaceutical danazol particles in nanometer range.

Micronization of silybin by the emulsion solvent diffusion method.

Micronized silybin particles were successfully prepared by emulsion solvent diffusion method. Uniform spherical and rod-shaped particles with a mean size of 2.48 and 0.89 microm could be obtained using sodium dodecyl sulfate (SDS) concentration of 0.1 wt% at 30 and 15 degrees C, respectively. The characterization of silybin particles by SEM and particle size distribution (PSD) indicated that with the increase of temperature from 15 to 30 degrees C, the as-prepared particles became bigger and had a tendency to turn into spherical shapes; with the increase of SDS concentration from 0.02 to 0.1 wt%, the span of PSD became narrower while the mean particle size kept almost unchanged. XRD patterns and FT-IR spectra showed that the spherical and rod-shaped silybin particles possessed decreased crystallinity; however, the chemical structure and components were similar to those of the commercial silybin powder. Dissolution tests demonstrated that both of the spherical and rod-shaped silybin particles exhibited significantly enhanced dissolution rate when compared to the commercial silybin powder.

Liquid antisolvent preparation of amorphous cefuroxime axetil nanoparticles in a tube-in-tube microchannel reactor

This article presents the preparation of nanoparticles of amorphous cefuroxime axetil (CFA) in a microporous tube-in-tube microchannel reactor (MTMCR). The experimental results indicated that CFA particle with a tunable size of 400-1400 nm could be achieved under a high throughput in the range of 1.5-6L/min. The average particle size decreased with increasing overall volumetric flow rate and decreasing CFA concentration, micropore size, and annular channel width. The produced CFA nanoparticles were characterized by SEM, XRD, FT-IR, DSC and a dissolution test, which indicated that the nanosized CFA was amorphous and exhibited higher dissolution rate compared to the raw CFA. The MTMCR might offer a general and facile pathway for mass production of the nanoparticles of hydrophobic pharmaceuticals thanks to its high throughput capacity and excellent micromixing performance.

Poly(lactic acid)/chitosan hybrid nanoparticles for controlled release of anticancer drug.

Poly(lactic acid) (PLA) is a kind of non-toxic biological materials with excellent absorbability, biocompatibility and biodegradability, which can be used for drug release, tissue engineering and surgical treatment applications. In this study, we prepared chitosan modified PLA nanoparticles as carriers for encapsulation of docetaxel by anti-solvent precipitation method. The morphology, particle size, zeta potential and composition of the PLA/chitosan were characterized by SEM, DLS, FTIR and XPS. As-prepared PLA/chitosan particles exhibited average size of 250 nm and showed very narrow distribution with polydispersity index of 0.098. Their large surface charge-ability was confirmed by zeta potential value of 53.9 mV. Docetaxel was released from PLA/chitosan nanoparticles with 40% initial burst release in 5 h and 70% cumulative release within 24 h, while from PLA nanoparticles 65% of docetaxel was released in 5h. In vitro drug release study demonstrated that PLA/chitosan nanoparticles prolonged drug release and decreased the burst release over the unmodified PLA nanoparticles. These results illustrated high potential of chitosan modified PLA nanoparticles for usage as anticancer drug carriers.

Engineering drug ultrafine particles of beclomethasone dipropionate for dry powder inhalation

Beclomethasone dipropionate (BDP), which is a member in the inhaled glucocorticosteroid class, is commonly used in the treatment of asthma by pulmonary delivery. The purpose of this study is to prepare ultrafine BDP particles for dry powder inhalation (DPI) administration by combining microfluidic antisolvent precipitation without surfactant, high-pressure homogenization (HPH) and spray drying. T-junction microchannel was adopted for the preparation of needle-like BDP particles. The needle-like particles could be easily broken down into smaller particles during HPH, which were assembled into uniform low-density spherical BDP aggregates by spray drying. The effects of the operation parameters, such as the flow rates of BDP methanol solution and antisolvent, the overall flow rate, the BDP concentration, and the change of the injection phase on BDP particle size were explored. The results indicated that the BDP particle size greatly decreased with the reduction of BDP solution flow rate and the increase of antisolvent flow rate. However, the BDP particle size firstly decreased and then increased with the increase of the overall flow rate and the increase of BDP concentration. Also, BDP solution as the injection phase could form the smaller BDP particles. 10 HPH cycles are enough to forming short rod-like particles. After spray drying, the BDP spherical aggregates with a 2-3 μm size could be achieved. They have an excellent aerosol performance, 2.8 and 1.4 times as many as raw BDP and vacuum-dried BDP particles, respectively.

Studies of Bicalutamide–Excipients Interaction by Combination of Molecular Docking and Molecular Dynamics Simulation

While the effects of hydrophilic excipients in enhancing the dissolution rate of water-insoluble drugs have been validated, the underlying mechanism remains poorly understood, particularly at a molecular level. In this work, a combination of docking calculations and MD simulations was applied to investigate the molecular interactions between bicalutamide (BIC) and each of three excipients: lactose (LAC), hydroxypropyl methylcellulose (HPMC), and mannitol (MAN). The calculated results indicated that BIC interacted with HPMC and MAN mainly by Lennard-Jones (LJ) interactions but with LAC mainly by Coulomb (Coul) interactions. There was no hydrogen bond formed between BIC and excipient. It was shown that BIC/LAC had the biggest total solvent accessible surface area with the biggest hydrophilic area and formed the most hydrogen bonds between excipient and water. In addition to the structure analyses, BIC/LAC had both the lowest interaction energy between BIC and excipient and the lowest interaction energy between BIC/excipient and water. All these led to the best dissolution performance of BIC/LAC, which could correspond to the experimental results of dissolution test. The present study suggests that a combination of docking calculations and MD simulations, which aims at complementing the experimental work, could provide a molecular insight into the interaction between drug and excipient. It also holds the great potential to simplify the optimization process of drug delivery system and reduce both time and costs.

Preparation of ultrafine fenofibrate powder by solidification process from emulsion

The solidification process from emulsion, which consisted of emulsifier, water and molten drug as oil phase without use of any organic solvent, was firstly employed to prepare ultrafine fenofibrate (FF) powder. The effects of stirring speed and volume ratios of hot emulsion to cold water on the particle size and morphology were discussed as well as the impacts of different emulsifiers on emulsion. The produced ultrafine powder was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, specific surface area analysis and a dissolution test. XRD patterns and FT-IR spectra showed that the ultrafine FF was crystalline powder with the structure and the components similar to those of bulk drug. The product had a mean particle size of about 3 microm with a narrow distribution from 1 microm to 5 microm. The specific surface area reached up to 6.23 m(2)/g, which was about 25 folds as large as that of bulk FF. In the dissolution tests, about 96.1% of ultrafine FF was dissolved after 120 min, while there was only 38.1% of bulk drug dissolved, proving that the dissolution property of ultrafine FF was significantly improved when compared to commercial drug.