Preparation,characterization, and in vivo evaluation of insulin-loaded PLA–PEG microspheres for controlled parenteral drug delivery

Aim: The aim of this study was to prepare insulin-loaded poly(lactic acid)–polyethylene glycol microspheres that could control insulin release at least for 1 week and evaluate their in vivo performance in a streptozotocin-induced diabetic rat model. Methods: The microspheres were prepared using a water-in-oil-in-water double emulsion solvent evaporation technique. Different formulation variables influencing the yield, particle size, entrapment efficiency, and in vitro release profiles were investigated. The pharmacokinetic study of optimized formulation was performed with single dose in comparison with multiple dose of Humulin® 30/70 as a reference product in streptozotocin-induced diabetic rats. Results: The optimized formulation of insulin microspheres was nonporous, smooth-surfaced, and spherical in structure under scanning electron microscope with a mean particle size of 3.07 ×μm and entrapment efficiency of 42.74% of the theoretical amount incorporated. The in vitro insulin release profiles was characterized by a bimodal behavior with an initial burst release because of the insulin adsorbed on the microsphere surface, followed by slower and continuous release corresponding to the insulin entrapped in polymer matrix. Conclusions: The optimized formulation and reference were comparable in the extent of absorption. Consequently, these microspheres can be proposed as new controlled parenteral delivery system.     

Preparation and characterization of theophylline loaded chitosan/β-cyclodextrin microspheres

The purpose of this project was to develop sustained release chitosan/β-cyclodextrin microspheres of theophylline (TH) prepared by spray drying method. The effect of several formulation variables on the characteristics of microspheres was studied. The B microspheres had a narrower particle size distribution with the diameter between l and 10 μm. SEM showed spherical microspheres with smooth or slightly wrinkled surfaces. FT-IR spectroscopy revealed that hydrogen bonds were formed between TH and chitosan or β-cyclodextrin. The drug entrapments significantly increased from 13.33 to 35.70% with an increase of the ratio of drug/polymer. The encapsulation efficiencies were from 85.16 to 91.40%. The in vitro release of TH from microspheres was related to the pH of the medium, swelling ability, especially in the ratio of drug/polymer. The B microspheres had a prolonged release pattern with the release rate of 60.20% (pH 6.8) within 8 h.     

Synthesis and characterization of hollow glass–ceramics microspheres

Hollow glass–ceramics microspheres (HGCMs), with the diameter from 10 to 60 μm and the shell thickness less than 2 μm, were successfully fabricated by a simple technique using polyacrylamide microspheres (PAMs) as template. The corresponding HGCM were obtained after a thermal treatment of the core–shell microspheres, which were synthesized with organic template method. The size, morphology and phase composition of synthesized products were determined via XRD, SEM, TGA. The effects of the amount of glass powder, the Hydrophile–Lipophile Balance (HLB) value, the sintering temperature, and the ratio of pre-adsorbed water to the water in the slurry on the morphologies of HGCM have been investigated. The results showed that the agglomeration of HGCM can be reduced by adjusting the HLB value. In addition, the amount of solid beads decreases obviously by reducing ratios and adjusting the HLB value. As the sintering temperature increases, the surface of the HGCM becomes smooth and compact. Meanwhile, computational investigations are carried out to better understand the strengthen effect of taking glass–ceramics materials in the system MgO–Al₂O₃–SiO₂ (MAS) as shell materials.     

Preparation and characterization of PEG–PPG–PEG copolymer/pregelatinized starch blends for use as resorbable bone hemostatic wax

In this study, polymer blends between PEG–PPG–PEG copolymer mixtures and pregelatinized starch at various compositions ranging from 0 to 3 % by weight were prepared and evaluated for potential use as novel resorbable bone hemostatic wax. It was found that the prepared samples had sufficient smearability for use as a bone wax. An addition of pregelatinized starch increased the hardness, smoothness and consistency of the texture while decreasing the adherence to glove. Thermal analysis indicated that the heat of fusion slightly decreased with increasing pregelatinized starch content. Compressive stiffness tended to decrease with increasing starch content for concentrations lower than 20 %, but re-increased at higher starch levels. In contrast, adherence deformation increased initially, but then decreased with increasing starch content. This behavior was related to the dependence of softening or reinforcing effect on the level of starch concentration in the samples. Adherence load and energy decreased with the addition of pregelatinized starch implying the decrease in adhesiveness of the samples. Furthermore, increasing the pregelatized starch amount also increased the liquid sealing duration of the samples at both 23 and 37 °C. Cytotoxicity tests against osteoblasts using a MTT assay revealed that the all the prepared samples and their raw materials did not show any cytotoxic potential. Formulations containing pregelatinized starch content between 20 and 30 % were found to show optimized performance.     

Preparation and characterization of polypropylene–wheat straw–clay composites

Preparation of polypropylene hybrid composite consisting of wheat straw and clay as reinforcement materials was investigated. The composite samples were prepared through melt blending method using a co-rotating twin-screw extruder. The composition of constituents of hybrid composite such as percentages of wheat straw, clay and maleic anhydride grafted polypropylene as a coupling agent was varied in order to investigate their influence on water absorption and flexural properties. The XRD analysis of composite samples containing clay showed shift in d₀₀₁ peak to lower 2θ indicating slight intercalation of polymer in clay sheets. The results of the study indicate that the increase in wheat straw and clay content in a composite increases the flexural modulus and reduces the resistance for water absorption. The increase in PP-MA coupling agent also increases the flexural modulus and resistance for water absorption. The morphological study by scanning electron microscope reveals that the addition of coupling agent increases the interfacial adhesion between the fibers and polymer matrix which is evidenced further from increased flexural modulus. Further, the particle size of wheat straw was analyzed before and after extrusion in order to investigate the effect of extrusion on wheat straw dimensions. The addition of clay as additional filler had no significant role on water absorption and flexural properties of the composite.     

Preparation and characterization of the carbon–Microsilica composite sorbent

In this paper, Microsilica, one kind of industry solid waste, was utilized firstly to prepare carbon–Microsilica composite sorbent with core–shell structures from a partial carbonization, mixture, and sulfonation process. The prepared composite sorbent was characterized with XPS, FT-IR, SEM, XRD and gas sorption experiments. The characterization results indicated BET surface area (S_BET) and total pore volume (V_total) of the prepared composite sorbent enhance 255% and 136% than Microsilica, respectively, and an abundant of oxygen functional groups, such as carboxyl and sulfonic groups, were introduced into the surface of the prepared composite sorbent. The adsorption capacity of the prepared composite sorbent for methylene blue (MB) and Cr(VI) also was investigated and compared with Microsilica and activated carbon, the results shown that the adsorption capacity of the prepared composite sorbent for methylene blue and Cr(VI) enhance 406.6% and 657.5% than Microsilica, and reach about 70.0% and 72.3% of activated carbon adsorption capacity, respectively. This paper proposed a new approach of comprehensive utilization of Microsilica with a uncomplicated process, and the prepared carbon–Microsilica composite sorbent with excellent adsorbent performance could be used as a potential substitute of activated carbon for heavy metal ion or organic dye adsorption in waste water.     

Preparation and characterization of BaTiO3–natural muscovite composites

Journal of Materials Science: Materials in Electronics - Natural muscovite (nM) exhibiting magnetic vortex states are ball milled into fine powder and mixed in different relative ratios (weight %)...     

Preparation and characterization of hydroxyapatite/polycaprolactone–chitosan composites

Hydroxyapatite (HA)/polycaprolactone (PCL)–chitosan (CS) composites were prepared by melt-blending. For the composites, the amount of HA was varied from 0% to 30% by weight. The morphology, structure and component of the composites were evaluated using environmental scanning electron microscope, X-ray diffraction and Fourier transform infrared spectroscope. The tensile properties were evaluated by tensile test. The bioactivity and degradation property were investigated after immersing in simulated body fluid (SBF) and physiological saline, respectively. The results show that the addition of HA to PCL–CS matrix tends to suppress the crystallization of PCL but improves the hydrophilicity. Adding HA to the composites decreases the tensile strength and elongation at break but increases the tensile modulus. After immersing in SBF for 14 days, the surface of HA/PCL–CS composites are covered by a coating of carbonated hydroxyapatite with low crystallinity, indicating the excellent bioactivity of the composites. Soaking in the physiological saline for 28 days, the molecular weight of PCL decreases while the mass loss of the composites and pH of physiological saline increase to 5.86% and 9.54, respectively, implying a good degradation property of the composites.     

Preparation and complex characterization of silica holmium sol–gel monoliths

Amorphous, sol–gel derived SiO₂ are known to biocompatible and bioresorbable materials. Biodegradable and inert materials containing radioactive isotopes have potential application as delivery vehicles of the beta radiation to the cancer tumors inside the body. Incorporation of holmium in the sol–gel derived SiO₂ could lead to the formation of a biodegradable material which could be used as carrier biomaterial for the radiation of radioactive holmium to the various cancer sites. The homogeneity of the prepared sol–gel silica holmium monoliths was investigated by Back Scattered Electron Imaging of Scanning Electron Microscope equipped with Energy Dispersive X-ray Analysis, X-ray Induced Photoelectron Spectroscopy and Nuclear Magnetic Resonance Spectroscopy. The biodegradation of the monoliths was investigated in Simulated Body Fluid and TRIS (Trizma pre-set Crystals) solution. The results show that by suitable tailoring of the sol–gel processing parameters holmium can be homogeneously incorporated in the silica matrix with a controlled biodegradation rate.     

Preparation and characterization of biomedical highly porous Ti–Nb alloy

The compressive strength and the biocompatibility were assessed for the porous Ti–25 wt%Nb alloy fabricated by the combination of the sponge impregnation technique and sintering technique. The alloy provided pore sizes of 300–600 μm, porosity levels of 71 ± 1.5 %, in which the volume fraction of open pores was 94 ± 1.3 %. The measurements also showed that the alloy had the compressive Young’s modulus of 2.23 ± 0.5 GPa and the strength of 98.4 ± 4.5 MPa, indicating that the mechanical properties of the alloy are similar to those of human bone. The scanning electron microscopy (SEM) observations revealed that the pores were well connected to form three-dimension (3D) network open cell structure. Moreover, no obvious impurities were detected in the porous structure. The experiments also confirmed that rabbit bone mesebchymal stem cells (MSCs) could adhere and proliferate in the porous Ti–25 wt%Nb alloy. The interactions between the porous alloy and the cells are attributed to the porous structure with relatively higher surface. The suitable mechanical and biocompatible properties confirmed that this material has a promising potential in the application for tissue engineering.     

5-Fluorouracil-loaded PLA/PLGA PEG–PPG–PEG polymeric nanoparticles: formulation,in vitro characterization and cell culture studies

In this study, 5-FU, a potent anticancer drug, is planned to be delivered via a new and promising drug delivery system, nanoparticles formed with hydrophobic core polymer and triblock copolymers; Poly(DL-lactic acid), Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PLA/PEG-PPG-PEG) and Poly(D,L-lactide–co-glycolide)/Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PLGA/PEG-PPG-PEG) nanoparticles. Particle size range of nanoparticles was found to be between 145 and 198?nm, which would promote the passive targeting of the nanoparticles to tumor cells based on the enhanced permeability and retention (EPR) effect. SEM images revealed all nanoparticles formulations to be spherical and without pores. Zeta potential, yield value and encapsulation efficiencies of 5-FU-loaded nanoparticles were within the range of ?11.1 and ?13.7?mV, 72.7–87.7% and 83.6–93.9%, respectively. Cumulative release of 5-FU was observed between 90% and 94.4% in all nanoparticle formulations by the end of 72?h, and fitness of release profiles to Higuchi model indicated matrix-controlled diffusion of the 5-FU from polymeric nanoparticles. Cell viability values of the cells treated with 5-FU-loaded nanoparticles were obtained as low as 47% and 52% with tetrazolium dye assay, suggesting that delivery of 5-FU via amphiphilic triblock copolymer nanoparticles would be a promising delivery system because of the EPR effect.     

Preparation and characterization of β-elemene-loaded microemulsion

Intravenously injectable emulsion of β-elemene was studied in detail. Both blank and β-elemene-loaded microemulsions were prepared using a simple water titration method. The pseudoternary phase diagram was constructed for the optimization of microemulsion. The loading capacity test, dilutability test, and especially the influence of antioxidants were conducted for further optimization of β-elemene-loaded microemulsion. Transmission electron microscope showed intact and spherical microemulsion droplets. Conductivity and viscosity measurements were used to study the phase behaviors of β-elemene-loaded microemulsions, providing convincing explanation. In vitro release study showed that β-elemene was steadily released until 12?h, which most fitted the first order.     

Preparation and characterization of β-elemene-loaded microemulsion

Intravenously injectable emulsion of β-elemene was studied in detail. Both blank and β-elemene-loaded microemulsions were prepared using a simple water titration method. The pseudoternary phase diagram was constructed for the optimization of microemulsion. The loading capacity test, dilutability test, and especially the influence of antioxidants were conducted for further optimization of β-elemene-loaded microemulsion. Transmission electron microscope showed intact and spherical microemulsion droplets. Conductivity and viscosity measurements were used to study the phase behaviors of β-elemene-loaded microemulsions, providing convincing explanation. In vitro release study showed that β-elemene was steadily released until 12?h, which most fitted the first order.     

Preparation of chitosan–hyaluronate double-walled microspheres by emulsification-coacervation method

Chitosan (CHS)−hyaluronate (HA) double-walled microspheres were prepared by emulsification-coacervation method. Tripolyphosphate (TPP) acted as ion crosslinker. The effects of oil/water volume ratio, surfactant, solution pH, TPP concentration, HA concentration, and emulsification time on microspheres fabrication and morphology were examined by Zeta (ζ) potential, Scanning electron microscopy (SEM) and Fourier-transform infrared spectrometry (FT-IR). It was found that TPP concentration, solution pH, surfactant and emulsification time were crucial factors for microspheres fabrication. Spherical microspheres with smooth surface were formed when TPP concentration was 8% or higher. The optimal pH for microspheres formation ranged from 6.0 to 7.0. As for surfactant, the microspheres obtained when span80 was applied alone were shapelier compared with those obtained when both span80 and tween80 were applied. With insufficient emulsification time, vacuous microcapsules, but not compact microspheres were formed. In addition, oil/water volume ratio and HA concentration also affected the microspheres morphology, but less importantly.     

Preparation and characterization of structure-tailored magnetic fluorescent Fe3O4/P(GMA–EGDMA–NVCz) core–shell microspheres

Fe₃O₄ nanoparticles were prepared by solvothermal reaction, and structure-tailored Fe₃O₄/poly(glycidyl methacrylate-ethyleneglycol dimethacrylate-N-vinylcarbazole) (Fe₃O₄/P(GMA–EGDMA–NVCz)) core–shell microspheres were achieved by distillation–precipitation polymerization of GMA, EGDMA, and NVCz in the presence of Fe₃O₄ nanoparticles. The properties of Fe₃O₄/P(GMA–EGDMA–NVCz) microspheres were characterized by transmission electron microscopy(TEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), and fluorescence spectroscopy. The results showed that the size of Fe₃O₄/P(GMA–EGDMA–NVCz) core–shell microspheres could be controlled to 930–470 nm by adjusting the amount of shell monomers, corresponding magnetic content of 45–82 wt%, and saturation magnetization of 32–63 emu/g. Moreover, the intensity of the fluorescence increased considerably with the decrease of shell thickness and the increase of NVCz concentration in the monomer mixture.     

Preparation and characterization of hollow Fe3O4/SiO2@PEG–PLA nanoparticles for drug delivery

In this study we present a novel targeted anticancer drug delivery, which was size controlled Fe₃O₄/SiO₂ hollow microspheres (HMS) as magnetic core and poly (ethylene glycol)-poly–(d,l-lactide) (PEG–PLA) surface coating (HMS@PEG–PLA). And investigations were to test a new convenient method, which is one-step precipitation polymerization on HMS, forming magnetic hollow polymer microspheres. The HMS@PEG–PLA which have hollow structure and uniform size were characterized by Transmission Electron Microscopy (TEM). Vibrating Sample Magnetometer (VSM) showed a characteristic of super paramagnetic with saturation magnetization value of about 19.78 emu/g. In vitro cytotoxicity of Fe₃O₄/SiO₂@PEG–PLA (HMS@PEG–PLA) hollow microspheres were of low toxicity, so it can be used as a drug carrier, and cisplatin (CDDP) as the model drug release behavior was researched. The results have exhibited preferable release properties.     

Preparation of alginate–CaCl2 microspheres as resveratrol carriers

Resveratrol-loaded calcium alginate microspheres for prolonged drug release were prepared by ionic gelation of alginate with calcium chloride (CaCl₂). Further, resveratrol-loaded calcium alginate microspheres were developed using two concentrations of alginate (0.5 and 1 % w/v) and CaCl₂ (0.5 and 1 M) and an encapsulator equipped with a 300-μm nozzle. The mean particle size of the microspheres was between 175.52 and 244.03 μm, and an encapsulation efficiency (EE) of over 95 % was observed. FTIR spectroscopy indicated a polyelectrolyte interaction between alginate and CaCl₂; alginate microsphere thermograms were analyzed by differential scanning calorimetry. X-ray diffraction shows the crystalline change of microspheres by cross linking. The release profiles and EE increased depending on the CaCl₂ concentration, and a slow initial burst release was observed on freeze-dried microspheres. These results indicate that resveratrol-loaded calcium alginate microspheres can be used as a potential resveratrol delivery system in the food industry.     

Synthesis and characterization of MeO–PEG–PLGA–PEG–OMe copolymers as drug carriers and their degradation behavior in vitro

The objective of this study was to characterize the methylpoly (ethylene glycol)-poly (lacticacid-co-glycolicacid)-poly (ethylene-glycol) (MeO-PEG-PLGA-PEG-OMe, abbreviation as PELGE) copolymers as intravenous injection drug delivery carriers and their degradation behavior in vitro. A series of MeO-PEG-PLGA-PEG-OMe copolymers with various molar ratios of lactic to glycolic acid and various molecular weights and different MeO-PEG contents were synthesized by ring-opening polymerization in the presence of MeO-PEG with molar masses of 2000 and 5000, using stannous octoate as the catalyst. The hydrophilicity of PELGE copolymers, evaluated by contact angle measurements, was found to increase with an increase in their MeO-PEG contents. Methylpoly (ethylene glycol)-poly (lacticacid-co-glycolicacid) (MeO-PEG-PLGA, abbreviation as PELGA) nanoparticles and PELGE nanoparticles were prepared using the emulsion-solvent evaporation technique (o/w) with Pluronic F68 (Poloxamer 188 NF) as emulsifier in the external aqueous phase. The degradation behavior of the nanoparticles was evaluated by the lactate generation with time upon their in vitro incubation in PBS (pH 7.4). The rate of in vitro degradation of the PELGE or PELGA nanoparticles depended on their composition, increasing with an increase in the proportion of MeO-PEG or LA in the copolymer chains. The degradation rate was slower at higher lactide: glycolide ratio. The lower the molecular weight of PELGE; the higher the degradation rate of the nanoparticles.     

Preparation and characterization of NASICON with a new sol–gel process

NASICON powders with the composition of Na₃Zr₂Si₂PO₁₂ were synthesized by using a sol–gel method. In the course of synthesis, a different material of oxalic acid was used to modify the synthesis process. The resulted precursors were sintered at the temperatures ranging from 700 to 1000 °C to get NASIOCN powders. X-ray diffractometer (XRD), IR and Raman spectra were employed to characterize the sintered products. Also, the ionic conductivity measurement conducted in the temperatures of 150–300 °C was used to evaluate their electronic properties. Furthermore, CO₂ sensor was prepared based on the pressed NASICON bulk. The relationship between its EMF response and the target gas concentration was checked. The experiment results showed that the NASICON material sintered at 900 °C possessed better properties in comparison with those sintered at other temperatures.