CeO2 nanoparticles synthesized by a microwave-assisted hydrothermal method: evolution from nanospheres to nanorods

Ceria (CeO2) plays a vital role in emerging technologies for environmental and energy-related applications. The catalytic efficiency of ceria nanoparticles depends on its morphology. In this study, CeO2 nanoparticles were synthesized by a microwave-assisted hydrothermal method under different synthesis temperatures. The samples were characterized by X-ray diffraction, transmission electron microscopy, Raman scattering spectroscopy, electron paramagnetic resonance spectroscopy and by the Brunauer-Emmett-Teller method. The X-ray diffraction and Raman scattering results indicated that all the synthesized samples had a pure cubic CeO2 structure. Rietveld analysis and Raman scattering also revealed the presence of structural defects due to an associated reduction in the valence of the Ce4+ ions to Ce3+ ions caused by an increasing molar fraction of oxygen vacancies. The morphology of the samples was controlled by varying the synthesis temperature. The TEM images show that samples synthesized at 80 degrees C consisted of spherical particles of about 5 nm, while those synthesized at 120 degrees C presented a mix of spherical and rod-like nanoparticles and the sample synthesized at 160 degrees C consisted of nanorods with 10 nm average diameter and 70 nm length. The microwave-assisted method proved to be highly efficient for the synthesis of CeO2 nanoparticles with different morphologies.

Successful Strategy for Targeting the Central Nervous System Using Magnetic Albumin Nanospheres

This study reports on the successful use of magnetic albumin nanosphere (MAN), consisting of maghemite nanoparticles hosted by albumin-based nanosphere, to target different sites within the central nervous system (CNS). Ultrastructural analysis by transmission electron microscopy (TEM) of the material collected from the mice was performed in the time window of 30 minutes up to 30 days after administration. Evidence found that the administered MAN was initially internalized and transported by erythrocytes across the blood-brain-barrier and transferred to glial cells and neuropils before internalization by neurons, mainly in the cerebellum. We hypothesize that the efficiency of MAN in crossing the BBB with no pathological alterations is due to the synergistic effect of its two main components, the iron-based nanosized particles and the hosting albumin-based nanospheres. We found that the MAN in targeting the CNS represents an important step towards the design of nanosized materials for clinical and diagnostic applications.

PLGA microspheres containing bee venom proteins for preventive immunotherapy

Bee venom (BV) allergy is potentially dangerous for allergic individuals because a single bee sting may induce an anaphylactic reaction, eventually leading to death. Currently, venom immunotherapy (VIT) is the only treatment with long-lasting effect for this kind of allergy and its efficiency has been recognized worldwide. This therapy consists of subcutaneous injections of gradually increasing doses of the allergen. This causes patient lack of compliance due to a long time of treatment with a total of 30-80 injections administered over years. In this article we deal with the characterization of different MS-PLGA formulations containing BV proteins for VIT. The PLGA microspheres containing BV represent a strategy to replace the multiple injections, because they can control the solute release. Physical and biochemical methods were used to analyze and characterize their preparation. Microspheres with encapsulation efficiencies of 49-75% were obtained with a BV triphasic release profile. Among them, the MS-PLGA 34 kDa-COOH showed to be best for VIT because they presented a low initial burst (20%) and a slow BV release during lag phase. Furthermore, few conformational changes were observed in the released BV. Above all, the BV remained immunologically recognizable, which means that they could continuously stimulate the immune system. Those microspheres containing BV could replace sequential injections of traditional VIT with the remarkable advantage of reduced number of injections. (C) 2011 Elsevier B.V. All rights reserved.

Tissue distribution of DNA-Hsp65/TDM-loaded PLGA microspheres and uptake by phagocytic cells

This study aimed to demonstrate that microspheres, used as delivery vehicle of DNA-Hsp65/TDM [plasmid DNA encoding heat shock protein 65 (Hsp65) coencapsulated with trehalose dimycolate (TDM) into PLGA microspheres], are widely spread among several organs after intramuscular administration in BALB/c mice. In general, we showed that these particles were phagocytosed by antigen presenting cells, such as macrophages and dendritic cells. Besides, it was demonstrated herein that draining lymph node cells presented a significant increase in the number of cells expressing costimulatory molecules (CD80 and CD86) and MHC class II, and also that the administration of the DNA-Hsp65/TDM and vector/TDM formulations resulted in the up-regulation of CD80, CD86 and MHC class II expression when compared to control formulations (vector/TDM and empty). Regarding the intracellular trafficking we observed that following phagocytosis, the microspheres were not found in the late endosomes and/or lysosomes, until 15 days after internalization, and we suggest that these constructions were hydrolysed in early compartments. Overall, these data expand our knowledge on PLGA [poly (lactic-co- glycolic acid)] microspheres as gene carriers in vaccination strategies, as well as open perspectives for their potential use in clinical practice.

Iron(III) porphyrin covalently supported onto magnetic amino-functionalized nanospheres as catalyst for hydrocarbon and herbicide oxidations

This work describes the covalent immobilization of an ironporphyrin, 5,10,15,20- tetrakis(pentafluorophenyl)porphyrin iron(III) chloride (FeTFPP), onto maghemite/silica magnetic nanospheres covered with aminofunctionalized silica. The resulting material (γ-Fe2O3/SiO2-NHFeP) was characterized by diffuse reflectance infrared spectroscopy (DRIFTS) and UV-Vis absorption spectroscopy. The catalytic activity of this magnetic ironporphyrin was investigated in the oxidation of hydrocarbons (styrene, (Z)-cyclooctene and R-(+)-limonene) and an herbicide (simazine) by hydrogen peroxide or 3-chloroperoxybenzoic acid. Hydrocarbon and simazine oxidation reaction products were analyzed by gas chromatography (GC) and high performance liquid chromatography (HPLC), respectively. This catalytic system proved to be efficient and selective for hydrocarbon oxidation, leading to high product yields from styrene (89%), cyclooctene (71%) and R-(+)-limonene (86%). Simazine oxidation was attained with 100% selectivity for a dechlorinated product (OEAT), while several oxidation products were obtained for the same catalyst in homogeneous media. The catalyst can be easily recovered through application of an external magnetic field and washed after reaction. Catalyst reuse experiments for R-(+)-limonene oxidation have shown that the catalytic activity is kept at 90% after 10 consecutive reactions.

The effect of complexation on characteristics and drug release from PLGA microspheres loaded by cyclosporine-cyclodextrin complex

The purpose of this study was to evaluate the effect of cyclosporine (CyA)-cyclodextrin (CD) complex incorporated within PLGA inicrospheres on microsphere characteristics, with particular emphasis on drug release kinetics. For this purpose, microspheres encapsulated with CyA and those loaded by CyA-CD complex were prepared by solvent evaporation and multiple emulsification solvent evaporation methods, respectively. Morphology, size, encapsulation efficiency and drug release pattern from microspheres were evaluated. Also, physicochemical properties of drug inside microspheres were characterized by differential scanning calorimetry (DSC) and infrared spectroscopy (IR) studies. Scanning electron microscopy (SEM) studies showed that microspheres encapsulated with CyA had islands on the microsphere surface but the islands were not seen on the surface of microspheres loaded by complex. Size range varied from 1 to 25 mu m for CyA encapsulated microspheres and 1 to 50 mu m for complex loaded microspheres. The release of CyA was biphasic with an initial more rapid release phase followed by a slower phase but drug release was twice as fast for complex loaded microspheres. IR studies did not indicate any chemical interaction between the components of microspheres and DSC thermograms revealed that CyA was present either in its amorphous state in microspheres or the presence of CyA as an inclusion complex within microspheres loaded by complex. In conclusion, using CyA as an inclusion complex with CD within microspheres can affect microsphere characteristics and drug release and it is possible to modify microsphere properties like drug release by incorporating CDs as complexing agents.

PLGA microspheres for the delivery of a novel subunit TB vaccine

Biodegradable poly(dl-lactide-co-glycolide) microspheres were prepared using a modified double emulsion solvent evaporation method for the delivery of the subunit tuberculosis vaccine (Ag85B-ESAT-6), a fusion protein of the immunodominant antigens 6-kDa early secretory antigenic target (ESAT-6) and antigen 85B (Ag85B). Addition of the cationic lipid dimethyl dioctadecylammonium bromide (DDA) and the immunostimulatory trehalose 6,6'-dibehenate (TDB), either separately or in combination, was investigated for the effect on particle size and distribution, antigen entrapment efficiency, in vitro release profiles and in vivo performance. Optimised formulation parameters yielded microspheres within the desired sub-10 mu m range (1.50 +/- 0.13 mu m), whilst exhibiting a high antigen entrapment efficiency (95 +/- 1.2%) and prolonged release profiles. Although the microsphere formulations induced a cell-mediated immune response and raised specific antibodies after immunisation, this was inferior to the levels achieved with liposomes composed of the same adjuvants (DDA-TDB), demonstrating that liposomes are more effective vaccine delivery systems compared with microspheres.

The fabrication of biodegradable nanospheres from novel hydroxalkanoates for the delivery of actives of pharmaceutical and agricultural interest

This work describes the fabrication of nanospheres from a range of novel polyhydroxyalkanoates supplied by Monsanto, St Louis, Missouri, USA for the delivery of selected actives of both pharmaceutical and agricultural interest. Initial evaluation of established microsphere and nanosphere fabrication techniques resulted in the adoption and optimisation of a double sonication solvent evaporation method involving the synperonic surfactant F68. Nanospheres could be consistently generated with this method. Studies on the incorporation and release of the surrogate protein Bovine Serum Albumin V demonstrated that BSA could be loaded with between 10-40% w/w BSA without nanosphere destabilisation. BSA release from nanospheres into Hanks Balanced Salts Solution, pH 7.4, could be monitored for up to 28 days at 37°C. The incorporation and release of the Monsanto actives - the insecticide Admire® ({ 1-[(6-chloro-3-pyridinyl)methyIJ-N-nitro-2-imidazolidinimine}) and the plant growth hormone potassium salt Gibberellic acid (GA3K) from physico-chemically characterised polymer nanospheres was monitored for up to 37 days and 28 days respectively, at both 4°C and 23°C. Release data was subsequently fitted to established kinetic models to elaborate the possible mechanisms of release of actives from the nanospheres. The exposure of unloaded nanospheres to a range of physiological media and rural rainwater has been used to investigate the role polymer biodegradation by enzymatic and chemical means might play in the in vivo release of actives and agricultural applications. The potential environmental biodegradation of Monsanto polymers has been investigated using a composting study (International Standard ISO/FDIS 14855) in which the ultimate aerobic biodegradation of the polymers has been monitored by the analysis of evolved carbon dioxide. These studies demonstrated the potential of the polymers for use in the environment, for example as a pesticide delivery system.

Effects of ball-milling on PLGA polymer and its implication on lansoprazole-loaded nanoparticles

PLGA is a biodegradable polymer utilised widely in pharmaceutical research for the encapsulation of a wide range of drugs as nano particulate systems. This study investigates the impact of rotary ball milling on the physical properties of PLGA and its influence on nanoparticle formation prepared using the solvent displacement technique. By applying mechanical stress to the polymer and altering its physical appearance and molecular weight, the loading of lansoprazole within the nanoparticles was increased to 96%, with a reduction in particle size. The results indicate that rotary ball milling significantly reduces particle size, increases lansoprazole loading and improves the release profile for lansoprazole loaded PLGA nanoparticles.

Cationic Bovine Serum Albumin (CBA) conjugated Poly Lactic-co-Glycolic Acid (PLGA) nanoparticles for extended delivery of methotrexate into brain tumor

Current treatment strategies for the treatment of brain tumor have been hindered primarily by the presence of highly lipophilic insurmountable blood-brain barrier (BBB). The purpose of current research was to investigate the efficiency of engineered biocompatible polymeric nanoparticles (NPs) as drug delivery vehicle to bypass the BBB and enhance biopharmaceutical attributes of anti-metabolite methotrexate (MTX) encapsulated NPs. The NPs were prepared by solvent diffusion method using cationic bovine serum albumin (CBA), and characterized for physicochemical parameters such as particle size, polydispersity index, and zeta-potential; while the surface modification was confirmed by FTIR, and NMR spectroscopy. Developed NPs exhibited zestful relocation of FITC tagged NPs across BBB in albino rats. Further, hemolytic studies confirmed them to be non-toxic and biocompatible as compared to free MTX. In vitro cytotoxicity assay of our engineered NPs on HNGC1 tumor cells proved superior uptake in tumor cells; and elicited potent cytotoxic effect as compared to plain NPs and free MTX solution. The outcomes of the study evidently indicate the prospective of CBA conjugated poly (D,L-lactide-co-glycolide) (PLGA) NPs loaded with MTX in brain cancer bomber with amplified capability to circumvent BBB.

Investigation of properties affecting controlled release of macromolecules from PLGA microspheres

Poly(lactide-co-glycolide), or PLGA, microspheres offer a widely-studied biodegradable option for controlled release of therapeutics. An array of fabrication methodologies have been developed to produce these microspheres with the capacity to encapsulate therapeutics of various types; and produce microspheres of a wide range of sizes for different methods of delivery. The encapsulation, stability, and release profiles of therapeutic release based on physical and thermodynamic properties has also been studied and modeled to an extent. Much research has been devoted to tailoring formulations for improved therapeutic encapsulation and stability as well as selective release profiles. Despite the breadth of available research on PLGA microspheres, further analysis of fundamental principles regarding the microsphere degradation, formation, and therapeutic encapsulation is necessary. This work aims to examine additional fundamental principles related to PLGA microsphere formation and degradation from solvent-evaporation of preformed polymer. In particular, mapping the development of the acidic microenvironment inside the microsphere during degradation and erosion is discussed. Also, the effect of macromolecule size and conformation is examined with respect to microsphere diameter and PLGA molecular weight. Lastly, the effects of mechanical shearing and protein exposure to aqueous media during microsphere formation are examined. In an effort to better understand the acidic microenvironment development across the microsphere diameter, pH sensitive dye conjugated to protein that undergoes conformational change at different acidic pH values was encapsulated in PLGA microspheres of diameters ranging from 40 µm to 80 µm, and used in conjunction with fluorescence resonance energy transfer to measure the radial pH change in the microspheres. Qualitative analysis of confocal micrographs was used to correlate fluorescence intensity with pH value, and obtain the radial pH across the center of the microsphere. Therapeutic encapsulation and release from polymeric microspheres is governed by an interconnected variety of factors, including the therapeutic itself. The globular protein bovine serum albumin, and the elongated and significantly smaller enzyme, lysozyme, were encapsulated in PLGA microspheres ranging from 40 µm to 80 µm in diameter. The initial surface morphology upon microsphere formation, release profiles, and microsphere erosion characteristics were explored in an effort to better understand the effect of protein size, conformation, and known PLGA interaction on the formation and degradation of PLGA microspheres and macromolecule release, with respect to PLGA molecular weight and microsphere diameter. In addition to PLGA behavior and macromolecule behavior, the effect of mechanical stresses during fabrication was examined. Two similar solvent extraction techniques were compared for the fabrication of albumin loaded microspheres. In particular, the homogeneity of the microspheres as well as capacity to retain encapsulated albumin were compared. This preliminary study paves the way for a more rigorous treatment of the effect of mechanical forces present in popular microsphere fabrication. Several factors affecting protein release from PLGA microspheres are examined herein. The technique explored for spatial resolution of the pH inside the microsphere proved mildly effective in producing a reliable method of mapping microsphere pH changes. However, notable trends with respect to microsphere size, PLGA molecular weight, and microsphere porosity were observed. Proposed methods of improving spatial resolution of the acidic microenvironment are also provided. With respect to microsphere formation, studies showed that albumin and lysozyme had little effect on the internal homogeneity of the microsphere. Rather, ionic interactions with PLGA played a more significant role in the encapsulation and release of each macromolecule. Studies also showed that higher instances of mechanical stress led to less homogeneous microspheres with lower protein encapsulation. This suggests that perhaps instead of or in addition to modifying the microsphere formation formulation, the fabrication technique itself should be more closely considered in achieving homogeneous microspheres with desired loading.