A facile synthetic route to aqueous dispersions of silver nanoparticles

Stable aqueous dispersions of silver nanoparticles have been synthesized from an organometallic precursor dissolved in an organic phase. Hydrogen gas is used to reduce the precursor to form silver nanoparticles which spontaneously transfer into an immiscible aqueous phase where they are stabilized. This route provides a simple pathway for the preparation of aqueous nanoparticle solutions and avoids production of the inorganic ions that are usually associated with aqueous methods. The effectiveness of a variety of aqueous stabilizing agents is evaluated. All products show plasmon absorption bands characteristic of silver nanoparticles and transmission electron microscopy reveals most particles to be below 40 nm in diameter.     

Stable aqueous dispersions of ZnO nanoparticles for ink-jet printed gas sensors

For the preparation of printed devices based on ZnO nanoparticles (ZnO NPs), stable colloidal dispersions of these materials are highly desirable. ZnO NPs have been synthesized by Chemical Vapor Synthesis. The particles have a spherical shape with a narrow size distribution. Stable aqueous dispersions of the ZnO NPs have been successfully prepared after the addition of a polymeric stabilizer. These stable dispersions have been used to print ZnO NP films on interdigital gold structures on silicon by ink-jet printing. The printing parameters have been optimized for forming layers with high quality. Close-packed ZnO NP thin films with a thickness between 100-250 nm have been prepared. Impedance spectroscopy has been used to study the gas sensing properties of the printed films at different temperatures in air and in hydrogen. The impedance spectra show the semi-circles typical for semiconducting materials. The conductance of the printed films has been measured at room temperature with high accuracy. In hydrogen gas, the conductance is larger as expected and this behavior is reversible.     

Functionalized solid lipid nanoparticles for transendothelial delivery

The objectives of this study were to synthesize and characterize functionalized solid lipid nanoparticles (fSLN) to investigate their interaction with endothelial cell monolayers and to evaluate their transendothelial transport capabilities. fSLN bearing tetramethylrhodamine-isothiocyanate-labeled bovine serum albumin (TRITC-BSA) and Coumarin 6 were prepared using a single-step phase-inversion process that afforded concurrent surface modification with a variety of macromolecules such as polystyrene sulfonate (PSS), poly-L-lysine (PLL), heparin (Hep), polyacrylic acid (PAA), polyvinyl alcohol, and polyethylene glycol (PEG). TRITC-BSA/Coumarin 6 encapsulated in fSLN with composite surface functionality (PSS-PLL and PSS-PLL-Hep) were also investigated. Size and surface charge of fSLN were analyzed using dynamic light scattering and transmission electron microscopy. Transport across bovine aortic endothelial cell (BAEC) monolayers was assessed spectrophotometrically using a transwell assay, and fSLN localization at the level of the cell and permeable support was analyzed using fluorescence microscopy. fSLN with tunable size and surface functionality were successfully produced, and had significant effects on cell localization and transport. Specifically, fSLN with PSS-PLL-Hep composite surface functionalization was capable of translocating 53.2 +/- 8.7 mug of TRITC-BSA within 4 h, with fSLN-PEG, fSLN-PAA, and fSLN-PSS exhibiting near-complete apical, paracellular, and cytosolic localization, respectively. Coumarin 6 was released by fSLN as indicated by dye labeling of BAEC membranes. We have developed a rapid process for the production of fSLN bearing low- and high-molecular-weight payloads of varying physicochemical properties. These findings have impications for drug delivery and bioimaging applications, since due to tunable surface chemistry, fSLN internalization and/or translocation across intact endothelial cell monolayers is possible.     

Preparation and characterization of camptothecin solid lipid nanoparticles

Camptothecin (CA), an antitumor drug, was incorporated into solid lipid nanoparticles (SLNs) prepared by high-pressure homogenization. A Taguchi orthogonal experimental design was used to study the influence of four different variables, with each variable having three value levels on nanoparticle size. Analysis of variance (ANOVA) has been used to evaluate the preparation of CA-SLNs and perform product optimization. The optimized CA-SLNs suspension was lyophilized using mannitol and glucose as cryoprotectants. The physicochemical characteristics of CA-SLNs were evaluated using transmission electron microscopy (TEM), electrophoresis, and differential scanning calorimetry (DSC). The release of camptothecin from CA-SLNs in various media was evaluated using a high-performance liquid chromatography (HPLC) method. The results showed that the concentration of emulsifier and the homogenization pressure had a significant influence on the particle size. The optimized CA-SLNs had an average diameter of about 200 nm, exhibited monodispersity with Dw/Dn of 1.06, and carried a negative charge. The optimal cryoprotectants consisted of 10% mannitol and 5% glucose in nanoparticle suspension. Lyophilized product was reconstituted in distilled water within 0.5 min without change of nanoparticle size. Camptothecin might exist in an amorphous state in SLNs. In vitro results showed that drug release was achieved for up to one week, and the released camptothecin quickly changed to open carboxylate form in the biological pH phosphate buffer. The results indicate that SLNs might be good potential sustained-release delivery vehicles for camptothecin or other lipophilic drugs.     

Mannosylated solid lipid nanoparticles for lung-targeted delivery of Paclitaxel

Objective: The present study discusses paclitaxel (PTX)-loaded mannosylated-DSPE (Distearoyl-phosphatidyl-ethanolamine) solid lipid nanoparticles (M-SLNs) using mannose as a lectin receptor ligand conjugate for lung cancer targeting and to increase the anticancer activity of PTX against A549 lung’s epithelial cancer cells.

Materials and methods: The PTX-SLNs were prepared by solvent injection method and mannose was conjugated to the free amine group of stearylamine. The M-SLNs obtained were characterized for their particle size, polydispersity index, zeta potential and morphology by transmission electron microscope.

Results: The M-SLNs were spherical in shape with 254?±?2.3?nm average size, positive zeta potential (3.27?mV), 79.4?±?1.6 drug entrapment efficiency and showed the lower extent of drug release 40% over 48?h in vitro. Cytotoxicity study on A549 cell lines and biodistrubtion study of drug revealed that M-SLNs deliver a higher concentration of PTX as compared to PTX-SLNs in an alveolar cell site.

Discussion and conclusion: These results suggested that mannosylated M-SLNs are safe and potential vector for lung cancer targeting.     

Preparation of continuous gold nanowires by electrospinning of high-concentration aqueous dispersions of gold nanoparticles

Gold nanowires are prepared by the electrospinning of highly concentrated aqueous dispersions of gold nanoparticles (AuNPs) in the presence of poly(vinyl alcohol) and subsequent annealing at higher temperatures. Continuous wires of sintered AuNPs are obtained as a result of this process. The Au wires are characterized by transmission electron microscopy, helium ion microscopy, optical microscopy, and X-ray diffractometry.     

Stabilizing ability of surfactant on physicochemical properties of drug nanoparticles generated from solid dispersions

This study was aimed to examine the nanoparticle formation from redispersion of binary and ternary solid dispersions. Binary systems are composed of various ratios of glibenclamide (GBM) and polyvinylpyrrolidone K30 (PVP-K30), whereas a constant amount at 2.5%w/w of a surfactant, sodium lauryl sulfate (SLS) or Gelucire44/14 (GLC), was added to create ternary systems. GBM nanoparticles were collected after the systems were dispersed in water for 15?min. The obtained nanoparticles were characterized for size distribution, crystallinity, thermal behavior, molecular structure, and dissolution properties. The results indicated that GBM nanoparticles could be formed when the drug content of the systems was lower than 30%w/w in binary systems and ternary systems containing SLS. The particle size ranged from 200 to 500?nm in diameter with narrow size distribution. The particle size was increased with increasing drug content in the systems. The obtained nanoparticles were spherical and showed the amorphous state. Furthermore, because of being amorphous form and reduced particle size, the dissolution of the generated nanoparticles was markedly improved compared with the GBM powder. In contrast, all the ternary solid dispersions prepared with GLC anomalously provided the crystalline particles with the size ranging over 5?µm and irregular shape. Interestingly, this was irrelevant to the drug content in the systems. These results indicated the ability of GLC to destabilize the polymer network surrounding the particles during particle precipitation. Therefore, this study suggested that drug content, quantity, and type of surfactant incorporated in solid dispersions drastically affected the physicochemical properties of the precipitated particles.     

Preparation and pharmacokinetic evaluation of Tashinone IIA solid lipid nanoparticles

Tashinone IIA loaded solid lipid nanoparticles (TA-SLN) coated with poloxamer 188 was prepared by emulsification/evaporation. The TA-SLN was characterized by transmission electron microscope and dynamic light scattering (DLS). The results showed that the TA-SLN had an average diameter of 98.7 nm with a zeta potential of - 31.6 mv and the drug loading of 4.6% and entrapment efficiency of 87.7%. In vitro release experiment showed that the release of Tashinone IIA from TA-SLN was in accordance with the Weibull equation. The best model fitting experimental data was a two-compartment open model with first-order. The area under curve of plasma concentration-time (AUC) and mean residence time (MRT) of TA-SLN were much higher than those of Tashinone IIA control solution (TA-SOL). The results of pharmacokinetic studies in rabbits indicated that the formulation of TA-SLN was successful in providing a delivery of slow release of Tashinone IIA.     

Anionic solid lipid nanoparticles supported on protamine/DNA complexes

The objective of this study was to design novel anionic ternary nanoparticles for gene delivery. These ternary nanoparticles were equipped with protamine/DNA binary complexes (150-200?nm) as the support, and the anionic formation was achieved by absorption of anionic solid lipid nanoparticles (≤20?nm) onto the surface of the binary complexes. The small solid lipid nanoparticles (SLNs) were prepared by a modified film dispersion-ultrasonication method, and adsorption of the anionic SLNs onto the binary complexes was typically carried out in water via electrostatic interaction. The formulated ternary nanoparticles were found to be relatively uniform in size (257.7 ± 10.6?nm) with a 'bumpy' surface, and the surface charge inversion from 19.28 ± 1.14?mV to -17.16 ± 1.92?mV could be considered as evidence of the formation of the ternary nanoparticles. The fluorescence intensity measurements from three batches of the ternary nanoparticles gave a mean adsorption efficiency of 96.75 ± 1.13%. Circular dichroism spectra analysis showed that the protamine/DNA complexes had been coated by small SLNs, and that the anionic ternary nanoparticles formed did not disturb the construction of the binary complexes. SYBR Green I analysis suggested that the ternary nanoparticles could protect the DNA from nuclease degradation, and cell viability assay results showed that they exhibit lower cytotoxicity to A549 cells compared with the binary complexes and lipofectamine. The transfection efficiency of the ternary nanoparticles was better than that of naked DNA and the binary complexes, and almost equal to that of lipofectamine/DNA complexes, as revealed by inversion fluorescence microscope observation. These results indicated that the anionic ternary nanoparticles could facilitate gene transfer in cultured cells, and might alleviate the drawbacks of the conventional cationic vector/DNA complexes for gene delivery in vivo.     

Processable aqueous dispersions of graphene nanosheets

Graphene sheets offer extraordinary electronic, thermal and mechanical properties and are expected to find a variety of applications. A prerequisite for exploiting most proposed applications for graphene is the availability of processable graphene sheets in large quantities. The direct dispersion of hydrophobic graphite or graphene sheets in water without the assistance of dispersing agents has generally been considered to be an insurmountable challenge. Here we report that chemically converted graphene sheets obtained from graphite can readily form stable aqueous colloids through electrostatic stabilization. This discovery has enabled us to develop a facile approach to large-scale production of aqueous graphene dispersions without the need for polymeric or surfactant stabilizers. Our findings make it possible to process graphene materials using low-cost solution processing techniques, opening up enormous opportunities to use this unique carbon nanostructure for many technological applications.     

Evaluation of solid dispersions of Clofazimine

Clofazimine (CLF) was formulated with polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) as a solid solid dispersion (SSD) to increase the aqueous solubility and dissolution rate of the drug. Different molecular weights of PEG (1500, 4000, 6000, and 9000 Da) and PVP (14,000 and 44,000 Da) were used in different drug:carrier weight ratios (1:1, 1:5, and 1:9) and their effect on the dissolution performance of the drug was evaluated in USP Type 2 apparatus using 0.1 N HCl medium. The dissolution rate was compared with corresponding physical mixtures, a currently marketed soft gelatin capsule product, and free CLF. The effect of different methods of preparation (solvent/melt) on the dissolution rate of CLF was evaluated for PEG solid dispersions. Saturation solubility and phase solubility studies were carried out to indicate drug:carrier interactions in liquid state. Infrared (IR) spectroscopy and X-ray diffraction (XRD) were used to indicate drug:carrier interactions in solid state. Improvement in the drug dissolution rate was observed in solid dispersion formulations as compared to the physical mixtures. The dissolution rate improved with the decreasing weight fraction of the drug in the formulation. Polyvinyl pyrrolidone solid dispersion systems gave a better drug release profile as compared to the corresponding PEG solid dispersions. The effect of molecular weight of the PEG polymers did not follow a definite trend, while PVP 14,000 gave a better dissolution profile as compared to PVP 44,000. Improvement in saturation solubility of the drug in the solid dispersion systems was noted in all cases. Further, IR spectroscopy indicated drug:carrier interactions in solid state in one case and XRD indicated reduction in the crystallinity of CLF in another. It was concluded that solid-dispersion formulations of Clofazimine can be used to design a solid dosage form of the drug, which would have significant advantages over the currently marketed soft gelatin capsule dosage form.     

Shrinkage phenomena in drying of natural organomineral dispersions

A procedure is suggested for simultaneous investigation of shrinkage and capillary pressures in drying of natural organomineral dispersions. Relations are studied that govern variations of internal forces in different stages of sapropel structure formation in the heat- and mass-transfer process. Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 71, No. 2, pp. 233–236, March–April, 1998.     

Studies on solid dispersions of nifedipine

Abstract

Nifedipine-Polyethylene glycol solid dispersions were prepared by melting or fusion method in order to improve nifedipine solubility in the aqueous body fluids. The dissolution rate of the drug was markedly increased in these solid dispersion systems. The increase in dissolution was a function of the ratio of drug to polyethylene glycol used and the molecular weight of polyethylene glycol. The dissolution rate was compared with a 10% w/w physical mixture of drug with polyethylene glycol.

The physical state of nifedipine after fusion was determined by X-ray crystallography on the pure drug and on the solidified melts. The X-ray diffraction studies indicated that nifedipine in the solid dispersion which was obtained by sudden cooling of the melt, was in the thermodynamically unstable metastable form. It was established that the slow cooling of the melt as well as powdering of solid dispersion resulted in the emergence of crystallinity.

The effect of aging on nifedipine-polyethylene glycol 6000 solid dispersions has been investigated. After storage at room temperature for six months, solid dispersions showed no change in the dissolution rate and the X-ray diffraction pattern showed slight enhancement in crystallinity.     

Studies on solid dispersions of nifedipine

Nifedipine-Polyethylene glycol solid dispersions were prepared by melting or fusion method in order to improve nifedipine solubility in the aqueous body fluids. The dissolution rate of the drug was markedly increased in these solid dispersion systems. The increase in dissolution was a function of the ratio of drug to polyethylene glycol used and the molecular weight of polyethylene glycol. The dissolution rate was compared with a 10% w/w physical mixture of drug with polyethylene glycol.

The physical state of nifedipine after fusion was determined by X-ray crystallography on the pure drug and on the solidified melts. The X-ray diffraction studies indicated that nifedipine in the solid dispersion which was obtained by sudden cooling of the melt, was in the thermodynamically unstable metastable form. It was established that the slow cooling of the melt as well as powdering of solid dispersion resulted in the emergence of crystallinity.

The effect of aging on nifedipine-polyethylene glycol 6000 solid dispersions has been investigated. After storage at room temperature for six months, solid dispersions showed no change in the dissolution rate and the X-ray diffraction pattern showed slight enhancement in crystallinity.     

Physicochemical characterization techniques for solid lipid nanoparticles: principles and limitations

Solid lipid nanoparticles (SLNs) are gaining importance due to numerous advantages they offer as a drug delivery system. SLN incorporate poorly soluble drugs, proteins, biologicals, etc. SLN are prepared by techniques like high-pressure homogenization, sonication and employs a wide range of lipids and surfactants. Physicochemical characterization techniques include particle size analysis, zeta potential and determination of crystallinity/polymorphism. Furthermore, drug loading and drug entrapment efficiency are common parameters used to test the efficiency of SLN. Most importantly, the functionality assay of SLN is essential to predict the activity and performance in vivo. The review presented discusses the importance of SLN in drug delivery with emphasis on principles and limitations associated with their physicochemical characterization.     

Histopathological evaluation of caffeine-loaded solid lipid nanoparticles in efficient treatment of cellulite

Context: Cellulite refers to dimpled appearance of the skin, usually located in the thighs and buttocks regions of most adult women.

Objective: The aim of this study was to formulate topically used caffeine-loaded solid lipid nanoparticle (SLN) for the treatment of cellulite.

Methods: SLNs were prepared by hot homogenization technique using Precirol® as lipid phase. The physical characterization and stability studies of SLNs as well as in vitro skin permeation and histological studies in rat skin were conducted.

Results: The mean particle size, encapsulation efficiency and loading efficiency percentages for optimized SLN formulation were 94?nm, 86 and 28%, respectively. In vitro drug release demonstrated that caffeine-loaded SLN incorporated into carbopol made hydrogel (caffeine-SLN-hydrogel) exhibited a sustained drug release compared to the caffeine hydrogel over 24?h. Caffeine-loaded SLNs showed a good stability during 12 months of storage at room temperature. The DSC and XRD results showed that caffeine was dispersed in SLN in an amorphous state. In vitro permeation studies illustrated higher drug accumulation in the skin with caffeine-SLN-hydrogel compared to caffeine hydrogel. The flux value of caffeine through rat skin in caffeine-SLN-hydrogel was 3.3 times less than caffeine hydrogel, representing lower systemic absorption. In contrast with caffeine hydrogel, the histological studies showed the complete lysis of adipocytes by administration of caffeine-SLN-hydrogel in the deeper skin layers.

Conclusion: Results of this study indicated that SLNs are promising carrier for improvement of caffeine efficiency in the treatment of cellulite following topical application on the skin.     

Characterization and body distribution of beta-elemene solid lipid nanoparticles (SLN)

Solid lipid nanoparticles (SLN) containing β-elemene, a volatile oil used for the treatment of cancer, were prepared by the method combining probe sonication and membrane extrusion. Effects of the formulations and procedures on the characteristics of SLN were investigated. Body distribution of β-elemene SLN in rats after intravenous administration was compared with that of the commercial emulsion. The results showed that dispersing the surfactant in the melted lipid matrix could obtain smaller particles than that dispersing in the water phase. Increasing the ratio of monostearin in the lipid matrix or the concentration of surfactant reduced the mean volume size of the SLN. Optimized formulation was composed of monostearin and precirol ATO 5 at a mass ratio of 3:7, which was quite stable for 8 months at room temperature. In vitro release of β-elemene from the SLN was slow and stable without obvious burst release and was found to follow the Higuich equation. After intravenous administration, the β-elemene levels after 5 min injection of SLN formulation were 1.5, 2.9, and 1.4 times higher than those of β-elemene emulsion in liver, spleen, and kidney, respectively, while the concentrations of β-elemene were decreased 30% in heart and lung. Therefore, the SLN containing β-elemene might be an attractive candidate for the treatment of liver cancer.     

Carbamazepine/betaCD/HPMC solid dispersions. II. Physical characterization

Solid dispersions containing carbamazepine (CBZ) associated with β-cyclodextrin (βCD) and/or hydroxypropyl methylcellulose were prepared by two different methods, spray-drying or physical mixture, and characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), infrared (IR) spectroscopy, and x-ray powder diffraction analysis (XRPD) studies. Scanning electron microscopy pictures showed that spray-drying produced a mixture of hollow, spherical, and partially shrunken microparticles of homogeneous materials, whereas the physical mixtures yielded heterogeneous systems in which all individual components could be identified. Thermal and IR analyses suggest the existence of a strong interaction between CBZ and excipients in spray-dried solid dispersions, but no CBZ polymorphic transition was detected by either IR spectroscopy or XRPD analysis after the spray-drying process.     

Preparation and characterization of solid lipid nanoparticles of furosemide using quality by design

The present work aimed to synthesize solid lipid nanoparticles (SLNs) of Furosemide (FRSM). The parameter sensitivity analysis showed a significant effect of particle size and reference solubility on the AUC_0–∞, C_max and t_max. The FRSM-encapsulated SLNs were synthesized by the phase inversion temperature (PIT) technique using 3² factorial design. The optimal level of 221.28?mg of Compritol 888 ATO and 420?mg of Cremophor RH 40 showed a mean hydrodynamic diameter (MHD) of 25.54?±?0.57?nm, a polydispersity index (PdI) of 0.158?±?0.01, the % entrapment efficiency of 80.70?±?4.06%, percent dissolution efficiency of 71.72?±?1.52% and time elapsed for 50% drug release of 3.67?±?0.15?h. The PIT was determined using the turbidity method and the values ranged between 75°C and 73°C. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) images represent spherical to sub-spherical and smooth surface of SLN. The Fourier transform-infrared (FTIR), differential scanning calorimetry (DSC) and x-ray diffraction (XRD) depict the drug-excipient compatibility. Korsmeyer–Peppas was found to be the best fit release kinetics model (R²?=?0.973; K-value?=?29.96 and release exponent?=?0.40), predicting the Fickian diffusion. The results advocate that the optimized formulation (OF) could promote the controlled release, and improve the physicochemical stability of the formulation. Hence, SLN could be a potential drug carrier for the peroral delivery of FRSM.     

Characterization and formulation optimization of solid lipid nanoparticles in vitamin K1 delivery

Background: Solid lipid nanoparticle (SLN) systems have been applied to various drugs and delivery routes. Vitamin K1 is an important cofactor for maintaining hemostasis and preventing hemorrhage. Method: Vitamin K1-loaded SLNs are systematically being developed by optimizing triglycerides and lipophilic and hydrophilic surfactants based on the size and stability of the resulting SLNs. Concentrations of the surfactants, Myverol and Pluronic, were optimized by a central composite design and response surface methodology. Vitamin K1 (phylloquinone) was used as a lipophilic drug in the SLN system to evaluate the potential for oral delivery. Results: Vitamin K1-loaded SLNs had a mean size of 125 nm and a zeta potential of ?23 mV as measured by photon correlation spectroscopy. The prepared SLNs were examined by differential scanning calorimetry and transmission electron microscopy and found to have an imperfect crystalline lattice and a spherical morphology. Effects of ultrasonication duration and drug load on the particle size and entrapment efficiency of the SLNs were also evaluated. Conclusion: More than 85% of the vitamin K1 was entrapped in SLNs when the payload was <5%. The vitamin K1 in SLNs was stable for a 54-h duration in simulated gastric and intestinal fluids. The particle size and vitamin K1 entrapped in the SLN were stable after 4 months of storage at 25°C. The results demonstrated that SLNs prepared herein can potentially be exploited as carriers for the oral delivery of vitamin K1.