In vitro evaluation of the effects of various additives and polymers on nerve growth factor microspheres

Objective: To evaluate the effects of various additives or polymers on the in vitro characteristics of nerve growth factor (NGF) microspheres.

Materials and methods: NGF microspheres were fabricated using polyethylene glycol (PEG), ovalbumin (OVA), bovine serum albumin (BSA) or glucose as protein protectors, and poly(lactide-co-glycolide) (PLGA) or poly(lactic acid) (PLA)/PLGA blends as encapsulation materials.

Results: Encapsulation efficiencies of the NGF microspheres with various additives or polymers were not more than 30%. A comparative study revealed that OVA was somewhat superior over others, and was thus chosen as the protective additive in subsequent experiments. Polymer analysis showed that NGF release from 1:1 PLA (η?=?0.8):PLGA (75/25, η?=?0.45) microspheres lasted for 90?d with a burst release rate of 12.7%. About 40% of the original bioactivity was retained on the 28th day, while 10% was left on the 90th day.

Discussion and conclusion: The combination of OVA as an additive and the PLA/PLGA blend as the coating matrix is suitable for encapsulation of NGF in microspheres for extended release.     

Impact of surfactant selection on the formulation and characterization of microparticles for pulmonary drug delivery

The effect of suspension stabilizers, internal aqueous phase volume and polymer amount were investigated for the production of protein loaded poly(d,l?lactide-co-glycolide) (PLGA) microparticles suitable for pulmonary drug delivery. PLGA microparticles were produced adopting water-in-oil-in-water (W/O/W) solvent evaporation technique and were investigated for surface morphology, particle size, encapsulation efficiency (EE%) and in-vitro release profile. Porous surface morphologies with a narrow size distribution were observed when employing 0.5?ml internal aqueous phase; 23.04?µm (±0.98), 15.05?µm (±0.27) and 22.89?µm (±0.41) for PVA, Tween 80 and oleic acid. Porous microparticles exhibited increased size and reduction in EE% with increasing internal aqueous phase, with non-porous microparticles produced when adopting 2.0?ml internal aqueous phase. The selection of stabilizer influences the size of the pores formed thus offers potential for the aerodynamic properties of the microparticles to be manipulated to achieve suitable aerosolization characteristics for pulmonary delivery of proteins.     

Self-assembly of silver nanoparticles into dendritic flowers from aqueous solution

Similar to folding of proteins into three-dimensional (3D) structure, self-assembly of metallic nanoparticles (NPs) into dendritic or other supramolecular structures is of greater interest, yet less understood. We observed spontaneous, template-free organisation of silver NPs into 3D, dendritic, elegant, flower-like structures from an aqueous solution containing AgNO₃ and L-cysteine (Cys). The resultant NPs and dendritic structures were characterised using UV–Vis spectroscopy and scanning and transmission electron microscopy. The process initiated most likely by diffusion-limited aggregation in the liquid phase, which were further grown into elegant, dendritic flowers probably by evaporation of residual wetting layer of larger NPs. Electrostatic attraction between –COO^? and –NH₃ ⁺ groups of L-Cys on the surface of silver NPs may also have a role in their growth.     

Formulation and characterization of ethylcellulose microparticles containing .l-alanyl- l-glutamine peptide

Context: The l-alanyl-l-glutamine peptide (AGP) has been effective to promote acute glycemia recovery during long-term insulin-induced hypoglycemia (IIH), and the oral administration of AGP is suggested to prevent prolonged hypoglycemia, such as nocturnal hypoglycemia.

Objective: Considering the ability of AGP on glycemia recovery and AGP’s fast metabolism, the aim of current study was to obtain and characterize ethylcellulose microparticles to deliver the drug for a prolonged time.

Materials and Methods: Microparticles were prepared by simple and double emulsification/hardening method and characterized by scanning electron microscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), Fourier transform infra-red (FTIR) and FT-Raman spectroscopy and in vitro release.

Results and Discussion: Spherical structures with a mean diameter between 9.30?µm and 13.19?µm were formed. TG analysis showed that the thermal stability of AGP was even more increased by encapsulation with ethylcellulose. In addition, TG, DSC, FTIR and FT-Raman analyses proved that AGP was encapsulated in a molecular way. Higher values of encapsulation efficiency were observed for the microparticles prepared by double emulsification (57.83–83.67%) than for those prepared by simple emulsification (18.37%). However, the last ones could release the peptide in a quicker and more extensive manner than those prepared by double emulsification.

Conclusion: For the first time, microparticles containing AGP were developed and exhibited prolonged in vitro release as well as protection to the drug, and it could be considered as a dosage form for patients who suffer from insulin-induced hypoglycemia and/or nocturnal hypoglycemia.     

Comment on the paper by J. Thomas Joseph Prakash, S. Kumararaman, “Growth and characterization of l-asparagine thiourea monohydrate (LATM): A nonlinear optical single crystal”, Materials Letters 62(2008) 4003-4005

It is argued that the conclusion of the authors of the title paper on obtaining of a new crystal l-asparagine thiourea monohydrate is erroneous. The authors actually have obtained well known l-asparagine monohydrate crystal.     

L-Aspartic acid/L-cysteine/gold nanoparticle modified microelectrode for simultaneous detection of copper and lead

This paper presents an electrochemical microsensor for simultaneous detection of copper (II) and lead (II) using an l-aspartic acid/l-cysteine/gold nanoparticle modified microelectrode. The microelectrode was fabricated by Micro Electro-Mechanical System technique. The complex of gold nanoparticles (AuNPs) and amino acid with carboxyl group was used as the selective ligand for metal ions. The microelectrode was firstly modified with AuNPs to increase the sensitive area of the working electrode. Subsequently, the AuNPs/gold electrode was modified with l-cysteine and then covalently linked with a monolayer of l-aspartic acid using glutaraldehyde. Electrochemical analysis of metal ions was achieved by using square wave voltammetry without stirring. The microsensor exhibited an excellent linear range from 5 μg L^− 1 to 2000 μg L^− 1 with the limit of detection of 1 μg L^− 1. This metal ion detection method based on l-aspartic acid/l-cysteine/gold nanoparticle modified microelectrode is simple, sensitive and it could be used for electrochemical analysis of copper (II) and lead (II).     

Facile, one-step controlled synthesis of Se nanocrystals in the presence of l-tyrosine

Se with different morphologies was synthesized using l-tyrosine as reducing agent and soft template by means of hydrothermal method. The method was simple and convenient to handle. The reaction process was monitored using ultraviolet-visible spectroscopy (UV-vis) and Fourier-transform infrared spectroscopy (FTIR). The morphology and crystalline phase were determined by transmission electron microscopy (TEM), scanning electronic microscopy (SEM) and X-ray diffraction (XRD) pattern. The results show that the morphologies and the crystalline phases of Se can be easily controlled. By varying the concentration ratio of l-tyrosine to selenious acid, the morphologies and crystalline phases of Se were not changed, but the diameter of Se was different. Se nano-rods are obtained in the lower temperature, and there is a transformation of microspheres into nanorods of Se with the increase of reaction time or reaction temperature. In addition, we discuss the possible mechanism of the reduction of SeO₃²⁻ ions by l-tyrosine. The eco-friendly, biogenic synthesis strategy could be widely used for preparing inorganic/organic biocomposites.     

Effect of Grinding on the Structure and Chemical Extraction of Metals from Serpentine

A serpentine mineral was treated in a planetary ball mill, and the effect of grinding was studied on the crystalline structure, average size, and metal extraction rate by sulfuric acid leaching. The crystalline peaks of the serpentine were gradually reduced with increase of grinding time, and after 120 min the serpentine turned into the amorphous phase. It was found that the extraction rate of the metals contained in the mineral by sulfuric acid was rapidly increased by the mechanochemical treatment. For the mineral treated for 240 min, Mg and Fe metal elements were extracted at 100% within 5 min, while 83% and 58% of Ca and Al, respectively, were obtained within 10 min. serpentine mechanochemical treatment leaching planetary ball mill amorphization     

The Role of Several l-HPCs in Preventing Tablet Capping During Direct Compression of Metronidazole

Several low-hydroxypropyl cellulose (l-HPC) derivatives (LH-11, 21, 22, 31, and 32) differing in granulometric particle size or in hydroxypropyl content were considered in the present study. The l-HPC grades were characterized as pure powders, in order to determine both compression and densification behavior, in presence or in absence of magnesium stearate as lubricant, and then, were physically mixed in different proportions with metronidazole, which was also previously characterized as pure powder. The tabletability and compressibility of these binary mixtures were then evaluated, in presence or in absence magnesium stearate as lubricant at two different compression speeds (20 and 70 mm/sec). It was observed that both binary mixture compression behavior and capping tendency were influenced by compression speed and by the presence of lubricant.

Differences in anti-capping efficiency between the l-HPCs may be related to their hydroxypropyl content. This parameter influences the interaction between the metronidazole and the polymer particles, and consequently the ability of the binary system to undergo densification under compression.     

A simple, low-temperature route to synthesize aqueous-dispersible Yb-Er co-doped hexagonal LaF3 nano-crystals for up-conversion fluorescence

Aqueous-dispersible Yb³⁺-Er³⁺ co-doped hexagonal LaF₃ nano-crystals were synthesized by a low-temperature aqueous phase approach in the presence of d-glucose. These nano-crystals are about 15-20 nm in rectangular shape and are easily dispersed in water, producing a transparent colloidal solution; they can also be precipitated and separated by the addition of NaOH. The morphology, crystal structure, fluorescence properties of these nano-crystals were analyzed by TEM, XRD, and spectroscopy, respectively. Furthermore, these nano-crystals exhibit red and green fluorescence in the visible spectral region when they are excited at 980 nm. The nano-crystals can be coated by a silica shell and their shape is not changed, which will be useful in the application of biological labeling.     

Preparation and microscopy examination of alginate-poly-l-lysine-alginate microcapsules

Ca-alginate-poly-l-lysine-alginate (APA-Ca) and Ba-alginate-poly-l-lysine-alginate (APA-Ba) microcapsules were prepared and their thickness and surface were examined by light microscopy and scanning electron microscopy. Specifically, light microscopy with frozen section was used to visualize and quantify the thickness of APA membrane, and monitor temporal changes in the thickness of microcapsules during a month long culture in vitro. The section graph of APA microcapsule represents the accurate measurement of layer thickness of APA-Ca with diameter 900?±?100 and 500?±?100?μm at 6.01?±?1.02 and 9.54?±?2.42?μm (p?p?in vitro. Field emission scanning electron microscopy with freeze drying method was used to detect the surface and thickness of dried microcapsules. From the results, the outer surface of APA-Ca and APA-Ba membrane were smooth and dense, the film thickness of the APA-Ca was about 450–690?nm, while the APA-Ba was approximately 335?nm. In vivo experiment, little significant difference was seen in the change of film thickness of microcapsules in intrapertioneal site for 30 days after transplantation (p?>?0.05), except that the recovery of APA-Ba was higher than the APA-Ca microcapsules. The paper showed an easy method to prepare APA-Ca and APA-Ba, and examine their thickness and surface, which could be utilized to study other types of microcapsules.     

Concentration dependence of solution crystallization for poly(l-lactide) in p-xylene

The macromolecular chain conformation in solution changes with the solvent and temperature, which will affect the formation of crystalline structure in the subsequent crystallization process. The crystallization behavior of poly(l-lactide) samples prepared from solutions with various concentrations was studied by differential scanning calorimetric and X-ray diffraction. It is found that the sample recovered from a dilute solution exhibits higher crystallinity, higher non-isothermal crystallization temperature and faster crystallization rate. The condensation process of polymer chain in dilute solutions has an influence on the crystallization of polymer in the solid state. This results in the acceleration of the melt crystallization rate and the rise of non-isothermal crystallization temperature of PLLA recovered from the dilute solution.     

Preliminary investigation on the design of biodegradable microparticles for ivermectin delivery: set up of formulation parameters

The aim was to design sterile biodegradable microparticulate drug delivery systems based on poly(dl-lactide) (PLA) and poly(?-caprolactone) (PCL) and containing ivermectin (IVM), an antiparasitic drug, for subcutaneous administration in dogs. The drug delivery system should: (i) ensure a full 12-month protection upon single dose administration; (ii) be safe with particular attention regarding IVM dosage and its release, in order to prevent over dosage side effects. This preliminary work involves: polymer selection, evaluation of the effects of γ-irradiation on the polymers and IVM, investigation and set up of suitable microparticle preparation process and parameters, IVM-loaded microparticles in vitro release evaluation.

Results of gel permeation chromatography analysis on the irradiated polymers and IVM mixtures showed that combination of IVM with the antioxidant α-tocopherol (TCP) reduces the damage extent induced by irradiation treatment, independently on the polymer type.

Solvent evaporation process was successfully used for the preparation of PLA microparticles and appropriately modified; it was recognized as suitable for the preparation of PCL microparticles. Good process yields were achieved ranging from 76.08% to 94.72%; encapsulation efficiency was between 85.76% and 91.25%, independently from the polymer used. The type of polymer and the consequent preparation process parameters affected microparticle size that was bigger for PCL microparticles (480–800?µm) and solvent residual that was >500?ppm for PLA microparticles. In vitro release test showed significantly faster IVM release rates from PCL microparticles, with respect to PLA microparticles, suggesting that a combination of the polymers could be used to obtain the suitable drug release rate.     

Facile and controllable one-step fabrication of selenium nanoparticles assisted by l-cysteine

A simple and solution-phase approach for large-scale synthesis of selenium nanoparticles (Nano-Se) by reducing sodium selenite (Na₂SeO₃) with l-cysteine has been demonstrated in this study. l-cysteine was used as both the reducing agent and surface modifier to control the formation of Nano-Se. The effects of reactant concentrations and ratios, and reaction time on the size and stability of Nano-Se were also investigated. The morphology and chemical composition of Nano-Se were characterized using various spectroscopic and microscopic methods. The results showed that varying the concentration ratio of l-cysteine to Na₂SeO₃ could control the diameter and morphology of Nano-Se, but not affecting their crystalline phases and chemical compositions. Monodisperse and homogeneous spherical Nano-Se with an average diameter of about 100 nm could be synthesized with the concentration ratio of l-cysteine to Na₂SeO₃ at 4:1. A striking feature of the as-synthesized Nano-Se was their good stability when dispersed in the reaction solutions, which indicates their potential in medical applications.     

Interlocked chitosan/poly(dl-lactide) blends

A novel processing method was developed to prepare chitosan/poly(dl-lactide) blends. These blends were further examined for their structures. SEM micrographs exhibited that under optimized processing conditions and with appropriate composition proportions, the resulting blends could possess interlocked internal microstructures. The results obtained from TGA and DMA measurements complementarily confirmed that two components could be well blended into a solid construct at a partially miscible level. The main mechanical properties of the blends were also investigated in both dry and hydrated states.     

Biomolecule-assisted synthesis of copper indium sulfide microspheres with nanosheets

Copper indium sulfide product was successfully synthesized via a mild solvothermal approach involving CuCl₂·2H₂O as the copper source, InCl₃ as the indium source, l-cysteine as the sulfur source and N,N-dimethylformamide as the reaction medium respectively at 200 °C for 12 h. Morphology, structure, and phase constituents of the as-prepared CuInS₂ powders were characterized by XRD, FE-SEM, XPS, and TEM (HRTEM). Results showed that the synthesized powder consists of microspheres made up of nanosheets and the thickness of the CuInS₂ nanosheets was found to vary from 50 to 100 nm. A possible formation mechanism was put forward and briefly discussed. The proposed solvothermal method using l-cysteine as the sulfur source offers a potential alternative avenue to prepare other ternary semiconductor nanomaterials.     

Investigating thermal degradation, crystallization and surface behavior of l-lactide, glycolide and trimethylene carbonate terpolymers used for medical applications

In this paper, the crystallization temperature (T_C), the melting temperature (T_m), the degradation mechanism and the surface properties of copolymers based on l-lactide, glycolide and trimethylene carbonate copolymers are investigated. The copolymers containing only l-lactide and trimethylene carbonate showed an endotherm peak in the DSC. Those containing three monomers (i. e. terpolymer) did not exhibit melting which may, otherwise, indicate the formation of an amorphous structure. The kinetic studies of thermal degradation in two different atmospheres using the FWO method revealed that single step degradation exists and the type of atmosphere (N₂ or O₂₎ has no influence on the degradation for these copolymers. The surface properties of the system showed that for the terpolymer containing trimethylene carbonate the contact angle of DDI water droplet on the polymer surface becomes smaller than that without TMC, vindicating inherent softness and stronger hydrophilic structure in the terpolymer.     

Ellipsometric determination of optical properties of carbazole-containing poly(l-glutamate) thin films prepared from different solvents

In this study, the refractive indices (n) and thicknesses of carbazole-containing hole-transport materials such as poly(γ-carbazolylethyl l-glutamate) (PCELG) and poly(N-vinyl carbazole) (PVCz) films were determined by carrying out ellipsometric measurements. The thicknesses of PCELG and PVCz films determined by ellipsometric analysis were in good agreement with those determined by surface profilometry. The dependence of the refractive indices of the PCELG films on film thickness was classified into two types on the basis of the solvent from which the films were prepared: the refractive indices either increased with increasing film thickness, as in the case of PCELG films prepared from 1,2-dichloroethane (DCE) and monochlorobenzene (?-Cl), or were independent of the film thickness, as in the case of films prepared from 1,1,2,2-tetrachloroethane (TCE). A comparison of these results with the structures of the polymers, as determined by ¹H NMR, reveals that the two types of dependences of the refractive indices of the PCELG thin film on the film thickness can be attributed to the two types of aggregation structures and/or orientational characteristics corresponding to the helical conformation of the polymer. In contrast, the refractive indices of PVCz films are governed mainly by the film thickness. Finally, we would like to emphasize that the combination of ellipsometry and other techniques such as NMR and surface profilometry provide information not only on the film thickness and refractive index but also on the aggregation structure in thin films with thicknesses on the order of 50 nm.     

In vitro bioactivity of chitosan/poly (d,l-lactide-co-glycolide) composites

Porous composites scaffolds of chitosan/poly(d,l-lactide-co-glycolide) were fabricated for tissue engineering applications by thermally induced phase separation and lyophilization techniques. The in vitro bioactivity evaluation of the scaffolds was carried out by analyzing the apatite layers produced on them using SBF as incubation medium. The apatite formation was analyzed using FTIR spectroscopy and Field emission scanning electron microscopy coupled to energy-dispersive electron X-ray spectroscopy. The cumulative results obtained from the IR spectra and SEM-EDS suggest that the developed composites might have potential applications in tissue engineering.