Yazhou Wang

Preparation of Eudragit L 100-55 enteric nanoparticles by a novel emulsion diffusion method.

In this study, a novel emulsion diffusion method was used to prepare enteric Eudragit L100-55 nanoparticles by ultrasonic dispersion and diffusion solidification. Omeprazole was selected as the model drug. The prepared nanoparticles were in spherical shape and exhibited negative zeta potential. The Fourier transform infrared spectroscopy results indicated that no molecular interaction occurred between the drug molecule and polymer chain. In addition, the nanoparticles showed a strong pH-sensitive release in vitro. A mild cytotoxicity of nanoparticle was observed in the subsequent studies, and the particle cellular uptake study showed that the nanoparticles could be taken up by Caco-2 cells after 0.5h incubation. Our results indicated that the enteric Eudragit L 100-55 nanoparticle could be synthesized successfully via this ultrasonic solidification method, which also could be applied to prepare other pH-sensitive polymer nanoparticles.

Cancer therapy based on nanomaterials and nanocarrier systems

Targeted delivery of drug molecules to tumor tissue is one of the most interesting and challenging endeavors faced in pharmaceutical field, due to the critical and pharmacokinetically specific environment that exists in tumor. Over these years, cancer targeting treatment has been greatly improved by new tools and approaches based on nanotechnology. The review firstly introduces the specific physical and chemical properties of a serial of nanomaterials, such as nanoparticles, micelles, dendrimers, carbon nanotubes, quantum dots, and nanofibers. It then places great emphasis on their application in the field of cancer therapy when they are used as nanocarrier systems. Based on the current status, the paper further discusses the unsolved problems and makes a perspective for the future prospects of the nanocarrier systems.

Rapid preparation of pH-sensitive polymeric nanoparticle with high loading capacity using electrospray for oral drug delivery.

Drug loading capacity is an important property for an ideal drug delivery system. However, the drug loading capacity of prepared pH-sensitive polymeric nanoparticles is usually low. To overcome this drawback, the electrospray method was used to prepare Eudragit L 100-55 nanoparticles with high drug loading capacity in one step. Omeprazole was selected as the model drug. The maximum loading capacity of nanoparticles was 43.21% by changing the mass ratio of drug to polymer, and the entrapment efficiency was nearly 100%. The prepared nanoparticle showed spherical or ellipsoidal morphology and the average diameter was about 300 nm. The pH-sensitive nanoparticle displayed pH-dependent release in vitro. In addition, a slight cytotoxicity was detected in the cytotoxicity study. The results indicated that electrospray is an easy, rapid and efficient technique for the preparation of high-loading pH-sensitive polymeric nanoparticles, and the pH-sensitive nanoparticle is a promising carrier for oral drug delivery.

APPLICATIONS OF ELECTROSPINNING TECHNIQUE IN DRUG DELIVERY

Electrospinning has proven to be a simple, versatile, and useful technique for fabricating nanofibers from a rich variety of functional materials. In the past few years, we have witnessed tremendous research progress in understanding electrospinning mechanisms and their applications in controlled drug releasing and delivery. In this review, a brief description of the electrospinning process and fiber formation mechanisms is first provided. Then, a detailed review and discussion are given of the creation of secondary structures on electrospun fibers, such as porous and core-shell or hollow fiber structures. Finally, the drug-loading methods and drug release control mechanisms for drug-loaded electrospun fibers are summarized and discussed.

Polymer-controlled core–shell nanoparticles: a novel strategy for sequential drug release

Sequentially-controlled drug release is required in cancer combination chemotherapy treatment. With the aim of co-delivering multiple drugs with different targets, immiscible and miscible liquids were utilized to fabricate PVP/PLGA and PCL/PLGA nanoparticles with a distinct core–shell structure by coaxial electrospray. It allows the fabrication of core–shell nanoparticles with different inner core characteristics of hydrophilic properties in one single step. The anti-angiogenesis agent combretastatin A4 (CA4) and doxorubicin (DOX) were each encapsulated separately in the core and shell parts of dual-drug nanoparticles. Both hydrophobic and hydrophilic drugs can be encapsulated into the coaxial-electrospray particles effectively, and the encapsulation efficiencies of drugs, particularly the hydrophilic ones, are over 90%. The endothelial cell and tumor cell co-culture systems were utilized to testify the performances of different nanoparticles against cytotoxicity, cellular apoptosis and VEGF and HIF-1α protein expressions in vitro. The melanoma cells B16-F10 and human umbilical vein endothelial cells (HUVECs) were sequentially targeted and killed by CA4 and DOX from these two kinds of nanoparticles. It demonstrated two different sequential drug release profiles in vitro. PVP/PLGA nanoparticles, with hydrophilic inner cores, presented a faster and higher drug release than that of PCL/PLGA nanoparticles, due to the better affinity of PVP polymers with the incubation media. These results suggested that the release rates and profiles of dual drug loaded particles can be tailored and tuned by choosing core polymers with different characteristics of hydrophilic properties. Therefore, the clinical treatment necessity can be fulfilled and the improvement of drug efficiency is promising in tumor combination chemotherapy.

Fabrication of core–shell micro/nanoparticles for programmable dual drug release by emulsion electrospraying

The study aimed at constructing a novel drug delivery system for programmable multiple drug release controlled with core–shell structure. The core–shell structure consisted of chitosan nanoparticles as core and polyvinylpyrrolidone micro/nanocoating as shell to form core–shell micro/nanoparticles, which was fabricated by ionic gelation and emulsion electrospray methods. As model drug agents, Naproxen and rhodamine B were encapsulated in the core and shell regions, respectively. The core–shell micro/nanoparticles thus fabricated were characterized and confirmed by scanning electron microscope, transmission electron microscope, and fluorescence optical microscope. The core–shell micro/nanoparticles showed good release controllability through drug release experiment in vitro. It was noted that a programmable release pattern for dual drug agents was also achieved by adjusting their loading regions in the core–shell structures. The results indicate that emulsion electrospraying technology is a promising approach in fabrication of core–shell micro/nanoparticles for programmable dual drug release. Such a novel multi-drug delivery system has a potential application for the clinical treatment of cancer, tuberculosis, and tissue engineering.

A novel gastroretentive porous microparticle for anti-Helicobacter pylori therapy: preparation, in vitro and in vivo evaluation.

Gastroretentive drug delivery system is a promising option for the treatment of Helicobacter pylori infection, which can prolong gastric residence time and supply high drug concentration in the stomach. In the present study, a low density system of metronidazole-loaded porous Eudragit® RS microparticle with high drug loading capacity (>25%) was fabricated via electrospray method. The porous structure and size distribution of microparticles were affected by polymer concentration and flow rate of solution. FTIR and XRD analyses indicated that drug has been entrapped into the porous microparticles. In addition, sustained release profiles and slight cytotoxicity in vitro were detected. Gamma scintigraphy study in vivo demonstrated that ¹³¹I-labeled microparticles retained in stomach for over 8h, and about 65.50% radioactive counts were finally detected in the region of interest. The biodistribution study confirmed that hotspot of radioactivity was remaining in the stomach. Furthermore, metronidazole-loaded porous microparticles can eradicate H. pylori completely with lower dose and administration frequency of antibiotic compared with pure drug, which were also more helpful for the healing of mucosal damages. These results suggest that prepared porous microparticle has the potential to provide better treatment for H. pylori infection.

Dual Drug Release from Core–Shell Nanoparticles with Distinct Release Profiles

Multiple drug combination is a promising strategy in biomedical fields, such as cancer chemotherapy and tissue engineering. With the aim of codelivering multiple drugs with different characteristics, immiscible and miscible liquids were utilized to fabricate nanoparticles of polyvinylpyrrolidone/poly(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone)/PLGA with distinct core-shell structure by coaxial electrospray. Each kind of nanoparticles can encapsulate the hydrophilic rhodamine B and hydrophobic naproxen in one single step efficiently. Encapsulation efficiency was over 85%. The different release patterns of dual-drug encapsulated were demonstrated when the drug location swapped, attributing to the distinct core-shell structures of nanoparticles and the interaction between drug molecules and carrier polymers. Meanwhile, the release profiles of encapsulated drugs with different loading amount were investigated as well. Dual drug release profiles from nanoparticles were affected by the unique architecture of nanocarriers (porous and core-shell structure), physical properties of polymers, and drugs. In addition, polymer-drug and drug-drug molecular interaction may take an important role in drug release behaviors. The results suggested that the distinct release kinetics of multiple drugs fabricated by coaxial electrospray can be obtained and tuned to fulfill the clinical requirement in combination therapy.

Development and assessment of kerateine nanoparticles for use as a hemostatic agent

Uncontrolled bleeding frequently occurs in some emergencies which can result in severe injury and even death. Keratin hydrogel has been found that it had good ahemostatic efficacy in the previous studies. However, an ideal hemostatic agent should not require mixing or preparation in advance, and hydrogel is not easy to store and carry. In the present study, the kerateine was firstly extracted from human hair, and then was prepared nanoparticles by a modified emulsion diffusion method. The synthesized nanoparticles showed spherical morphology with an average diameter of approximately 200 nm. The results of Fourier transform infrared spectroscopy and X-ray diffraction indicated that the chemical structure of kerateine did not change but the crystal form may be transformed in the nanoparticles. In addition, kerateine nanoparticles displayed a faster clotting time in vitro study than the kerateine extracts. Furthermore, kerateine nanoparticles significantly reduced the blood loss and coagulation time in the liver puncture and tail amputation in rat models. Our results indicated that kerateine nanoparticles could quickly form a high viscosity gel onto the wound and accelerate the blood coagulation based on their high specific surface area. Therefore, kerateine nanoparticles have great potential for hemostatic application.

Study of biocompatibility of medical grade high nitrogen nickel-free austenitic stainless steel in vitro

Adverse effects of nickel ions being released into the living organism have resulted in development of high nitrogen nickel-free austenitic stainless steels for medical applications. Nitrogen not only replaces nickel for austenitic structure stability but also improves steel properties. The cell cytocompatibility, blood compatibility and cell response of high nitrogen nickel-free austenitic stainless steel were studied in vitro. The mechanical properties and microstructure of this stainless steel were compared to the currently used 316L stainless steel. It was shown that the new steel material had comparable basic mechanical properties to 316L stainless steel and preserved the single austenite organization. The cell toxicity test showed no significant toxic side effects for MC3T3-E1 cells compared to nitinol alloy. Cell adhesion testing showed that the number of MC3T3-E1 cells was more than that on nitinol alloy and the cells grew in good condition. The hemolysis rate was lower than the national standard of 5% without influence on platelets. The total intracellular protein content and ALP activity and quantification of mineralization showed good cell response. We conclude that the high nitrogen nickel-free austenitic stainless steel is a promising new biomedical material for coronary stent development.