Hyper Rayleigh scattering of protein-mediated gold nanoparticles aggregates

The second harmonic generation response from protein-mediated gold nanoparticles assemblies in solution has been studied by the technique of hyper Rayleigh scattering (HRS). It is found that the HRS intensity from biotinylated bovine serum albumin coated gold nanoparticles is enhanced when StreptAvidin is added into the solution. This increase in intensity is attributed to the aggregation of the gold nanoparticles through the binding of biotin and StreptAvidin. Comparison with photo-absorption spectroscopy indicates that the technique of HRS is a potential tool in detecting small levels of particle aggregation in liquid samples.     

Determination of oligonucleotide ISIS 2922 in nanoparticulate delivery systems by capillary zone electrophoresis

ISIS 2922 is an antisense oligonucleotide with antiviral activity against cytomegalovirus. However, its rapid degradation in biological fluids and its low capacity for diffusion across cell membranes limit its therapeutical use. One possibility to overcome these drawbacks consists of using nanoparticles as drug carriers. The aim of this study was to develop an analytical method for determining the amount of ISIS 2922 loaded into albumin nanoparticles. For this purpose, capillary zone electrophoresis (CZE) was performed on a fused-silica capillary filled with borate buffer (12.5 mM, pH 9.5). Paracetamol was used as an internal standard and a diode-array detection system was set at 270 nm. Under these conditions, the limit of quantitation of ISIS 2922 was 1.27 microg and the precision and accuracy of the method did not exceed 7%. Moreover, the use of paracetamol as internal standard and the quantification by means of a 'corrected area' procedure enabled us to reduce the peak variability and accurately determine the amount of oligonucleotide loaded in the albumin nanoparticles. In summary, this assay is a selective and sensitive CZE method for the accurate quantitation of ISIS 2922 oligonucleotide in albumin nanoparticles.     

Functionalised, photostable, fluorescent polystyrene nanoparticles of narrow size-distribution

Fluorescent nanoparticles continue to be of wide interest, as they have many advantages over single fluorescent molecules for biological imaging and sensing applications, such as increased fluorescence intensity and reduced photobleaching. In the following work, styrene was copolymerised with a newly synthesised, fluorescein-based, vinylic crosslinking monomer, by emulsion polymerisation, to create a series of different sized fluorescent nanoparticles (35-100 nm), each of narrow size-distribution. The particles were found to be highly fluorescent and with lower photobleaching compared to fluorescein isothiocyanate (FITC), offering an attractive alternative. The fluorescence excitation and emission spectra were recorded, being similar to fluorescein, but with interesting variation in the excitation spectra. The particles also have a wide range of potential uses, such as examining particle uptake activity of a macrophage cell line, also demonstrated. The nanoparticles were coated with albumin to provide functionality for potential conjugation to biological targeting agents.     

Study on facile designing,swelling properties and structural relationship of gelatin nanoparticles

In the present work glutaraldehyde crosslinked gelatin (Type-A and Type-B) nanoparticles were fabricated following a microemulsion crosslinking technique. The structural, morphological, and stability features of nanoparticles were investigated using the techniques like FTIR, TEM, XRD, DLS, and surface charge measurements. The spectral peaks appeared in the FTIR spectra of gelatin nanoparticles confirmed the crosslinking of gelatin molecules with glutaraldehyde. The SEM analysis of the nanoparticles suggested that the size of gelatin nanoparticles was nearly 300 nm whereas the TEM analysis revealed their size around 200?nm. The size of nanoparticles was found to increase with increasing amounts of gelatin while it showed a decrease when the concentration of crosslinker was increased. An increase in percent crystallinity was observed when gelatin was crosslinked with glutaraldehyde. The water uptake capacity of the gelatin nanoparticles was evaluated under varying experimental conditions like, pH, temperature, presence of simulated physiological fluids and varying composition of the gelatin nanoparticles. To study the cytotoxic behavior of gelatin nanoparticles in vitro cytotoxicity analysis were performed. The gelatin nanoparticles demonstrated good stability and biocompatibility which suggested that these particles can be used as drug carrier in fabricating a swelling controlled drug delivery system.     

Reactivity of palladium nanoparticles supported on a microemulsion-based organogel network in supercritical carbon dioxide

Palladium (Pd) nanoparticles were prepared using the phase transfer method and coated with alkylamines as stabilizing agents stably dispersed in nonpolar solvents. Spherical Pd nanoparticles with an average diameter of 4 nm and a relatively narrow size distribution were obtained using hexylamine or dodecylamine, and they were successfully incorporated in microemulsion-based gelatin organogel (OG); also, an OG network containing Pd nanoparticles was prepared via drying. For the Mizoroki-Heck cross-coupling reaction of iodobenzene with methyl acrylate in supercritical carbon dioxide, the Pd nanoparticles in the OG network exhibited much higher reactivity than those in powder state. Preparation conditions of OG (e.g., gelatin concentration) affected the apparent reactivity of the supported Pd nanoparticles. The Pd nanoparticles in the OG network with high gelatin concentration were recycled with no appreciable change of reactivity. In contrast, the reactivity of the Pd nanoparticles with low gelatin concentration decreased during recycling.     

Stimuli‐responsive zein‐based nanoparticles as a potential carrier for ellipticine: Synthesis,release, and in vitro delivery

In the present research, we have investigated a drug delivery system based on the pH‐responsive behaviors of zein colloidal nanoparticles coated with sodium caseinate (SC) and poly ethylene imine (PEI). These systematically designed nanoparticles were used as nanocarriers for encapsulation of ellipticine (EPT), as an anticancer drug. SC and PEI coatings were applied through electrostatic adsorption, leading to the increased size and improved polydispersity index of nanoparticles as well as sustained release of drug. Physicochemical characteristics such as hydrodynamic diameter, size distribution, zeta potential and morphology of nanoparticles prepared using different formulations and conditions were also determined. Based on the results, EPT was encapsulated into the prepared nanoparticles with a high drug loading capacity (5.06%) and encapsulation efficiency (94.8%) under optimal conditions. in vitro experiments demonstrated that the release of EPT from zein‐based nanoparticles was pH sensitive. When the pH level decreased from 7.4 to 5.5, the rate of drug release was considerably enhanced. The mechanism of pH‐responsive complexation in the drug encapsulation and release processes was extensively investigated. The pH‐dependent electrostatic interactions and drug state were hypothesized to affect the release profiles. Compared to the EPT‐loaded zein/PEI nanoparticles, the EPT‐loaded zein/SC nanoparticles exhibited a better drug sustained‐release profile, with a smaller initial burst release and longer release period. According to the results of in vitro cytotoxicity experiments, drug‐free nanoparticles were associated with a negligible cytotoxicity, whereas the EPT‐loaded nanoparticles displayed a high toxicity for the cancer cell line, A549. Our findings indicate that these pH‐sensitive protein‐based nanoparticles can be used as novel nanotherapeutic tools and potential antineoplastic drug carriers for cancer chemotherapy with controlled release.     

Gelatin Nanoparticles with Enhanced Affinity for Calcium Phosphate

Gelatin nanoparticles can be tuned with respect to their drug loading efficiency, degradation rate, and release kinetics, which renders these drug carriers highly suitable for a wide variety of biomedical applications. The ease of functionalization has rendered gelatin an interesting candidate material to introduce specific motifs for selective targeting to specific organs, but gelatin nanoparticles have not yet been modified to increase their affinity to mineralized tissue. By means of conjugating bone‐targeting alendronate to biocompatible gelatin nanoparticles, a simple method is developed for the preparation of gelatin nanoparticles which exhibit strong affinity to mineralized surfaces. It has been shown that the degree of alendronate functionalization can be tuned by controlling the glutaraldehyde crosslinking density, the molar ratio between alendronate and glutaraldehyde, as well as the pH of the conjugation reaction. Moreover, it has been shown that the affinity of gelatin nanoparticles to calcium phosphate increases considerably upon functionalization with alendronate. In summary, gelatin nanoparticles have been developed, which exhibit great potential for use in bone‐specific drug delivery and regenerative medicine.

     

Pathways for Oral and Rectal Delivery of Gold Nanoparticles (1.7 nm) and Gold Nanoclusters into the Colon: Enteric-Coated Capsules and Suppositories

Two ways to deliver ultrasmall gold nanoparticles and gold-bovine serum albumin (BSA) nanoclusters to the colon were developed. First, oral administration is possible by incorporation into gelatin capsules that were coated with an enteric polymer. These permit the transfer across the stomach whose acidic environment damages many drugs. The enteric coating dissolves due to the neutral pH of the colon and releases the capsule’s cargo. Second, rectal administration is possible by incorporation into hard-fat suppositories that melt in the colon and then release the nanocarriers. The feasibility of the two concepts was demonstrated by in-vitro release studies and cell culture studies that showed the easy redispersibility after dissolution of the respective transport system. This clears a pathway for therapeutic applications of drug-loaded nanoparticles to address colon diseases, such as chronic inflammation and cancer.     

A high performance carrier for SnO2 nanoparticles used in lithium ion battery

Ferrocene-encapsulated single-walled carbon nanotubes (Fc@SWNTs) are developed as carriers for attaching SnO(2). When Fc@SWNTs coated with SnO(2) nanoparticles were used as anode material in lithium ion batteries, the reversible capacity remained over 900 mA h g(-1) after 40 cycles, much higher than other carbon nanomaterials.     

Preparation, characterization and application of pyrene-loaded methoxy poly(ethylene glycol)–poly(lactic acid) copolymer nanoparticles

Pyrene-loaded biodegradable polymer nanoparticles were prepared by incorporating pyrene into the polymer nanoparticles formulated from amphiphilic diblock copolymer, methoxy poly(ethylene glycol)–poly(lactic acid) (MePEG–PLA). Their morphological structure and physical properties were characterized by nuclear magnetic resonance (NMR), dynamic light scattering, fluorescence spectroscopy, transmission electronic microscopy and zeta potential measurements. Further, MePEG–PLA nanoparticles containing pyrene as fluorescent marker were administered intranasally to rats, and the distribution of nanoparticles in the nasal mucosa and the olfactory bulb were visualized by fluorescence microscopy. NMR results confirmed that MePEG–PLA copolymer can form nanoparticles in water, and hydrophilic PEG chains were located on the surface of the nanoparticles. The particle size, zeta potential and pyrene loading efficiency of MePEG–PLA nanoparticles were dependent on the PLA block content in the copolymer. Following nasal administration, the absorption of nanoparticles across the epithelium was rapid, with fluorescence observed in the olfactory bulb at 5 min, and a higher level of fluorescence persisted in the olfactory mucosa than that in the respiratory mucosa. These results show that pyrene could serve as a useful fluorescence probe for incorporation into polymer nanoparticles to study tissue distribution and MePEG–PLA nanoparticles might have a great potential as carriers of hydrophobic drugs.     

Cationic PLA nanoparticles for DNA delivery: comparison of three surface polycations for DNA binding, protection and transfection properties

Biodegradable cationic nanoparticles (cNP) made of poly(lactide) (PLA) have been shown to be promising carrier systems for in vivo DNA delivery and immunization. In previous work, we have described a versatile approach for the elaboration of cationic PLA cNP based on the use of pre-formed particles and subsequent adsorption of a model polycation, the poly(ethylenimine) (PEI). Here, we evaluated two more polycations, chitosan and poly(2-dimethyl-amino)ethyl methacrylate (pDMAEMA)) to determine the most suitable one for the development of PLA cNP as DNA carriers. Cationic PLA-PEI, PLA-chitosan and PLA-pDMAEMA nanoparticles were compared for interaction with plasmid DNA and, more importantly, with regards to the biological properties of bound DNA. pDMAEMA coating yielded the most positively charged nanoparticles with the highest DNA binding capacity (32 mg/g). Loaded with DNA, all three cNP were in the same size range ( approximately 500 nm) and had a negative zeta potential (-50 mV). PLA-chitosan was the only cNP that released DNA at pH 7; the two others required higher pH. Adsorption and release from cNP did not alter structural and functional integrity of plasmid DNA. Moreover, DNA coated onto cNP was partially protected from nuclease degradation, although this protection was less efficient for PLA-chitosan than others. The highest transfection efficiency in cell culture was obtained with PLA-pDMAEMA carriers. We have shown that at least three different cationic polymers (chitosan, PEI, pDMAEMA) can be used for the production of PLA-based particulate DNA carriers and most probably other cationic polymers can also be used in the same purpose. PLA-pDMAEMA cNP were the most promising system for DNA delivery in this in vitro study. Our future work will focus on the in vivo evaluation of these gene delivery systems.     

Surface Modification of Functional Nanoparticles for Controlled Drug Delivery

Abstract

Surface‐modified nanoparticles have received much attention as drug carriers. Natural and synthetic polymers are used as the materials to prepare nanoparticles and the properties of these nanoparticles originate with these polymeric materials. In particular, these nanoparticles are modified for specific objectives. The surface characteristics of (shell) nanoparticles are more important than those of the core, because the shell layer directly contacts body fluids and organs. Generally, the nanoparticles are coated with hydrophilic polymer to give long circulation and/or are conjugated with functional ligands or proteins for site‐specific delivery. In this review, the preparative methods and the applications of surface modification of polymeric functionalized nanoparticles for long‐circulation, site‐specific delivery, and oral delivery are discussed.     

Tannic acid-coated zeolite Y nanoparticles as novel drug nanocarrier with controlled release behavior and anti-protozoan activity against Trichomonas gallinae

In this study, a pH-sensitive drug release system was prepared by zeolite Y nanoparticles and tannic acid. Zeolite Y nanoparticles were synthesized via hydrothermal synthesis of colloidal suspensions and after that, were coated with tannic acid. In order to evaluate its performance, metronidazole as an anti-protozoan drug was loaded into nanocarriers via immersing method to study the in-vitro drug delivery behavior. This nanocomposite carriers represented pH-sensitive behavior and had more and faster release in acidic medium. In-vitro effects of metronidazole-loaded nanoparticles was measured against Trichomonas gallinae trophozoites in Trypticase Yeast extract Maltose medium. The results suggested that metronidazole-loaded and tannic acid-modified zeolite Y nanoparticles could be a potential anti-trichomonal agent.     

Synthesis and antitumoral activity of gelatin/polyoxometalate hybrid nanoparticles

Surfactant-free gelatin/heptamolybdate (HM) hybrid nanoparticles are prepared by a simple and environmentally friendly approach utilizing the electrostatic interaction between anionic HM and the zwitterionic gelatin. The obtained nanoparticles have a tunable size and very high HM loading content up to about 70%. In vitro and in vivo experiments prove that the gelatin/HM hybrid nanoparticles exhibit significantly better antitumor activity than plain ammonium heptamolybdate solution. Therefore, the gelatin/HM hybrid nanoparticles reported here may serve as a prototype platform for polymer/polyoxometalate (POM) hybrid nanoparticles as cancer treatment agents and hence open up more opportunities to maximize the potential of POM-based pharmaceutical agents.     

Surface plasmon mapping of dumbbell-shaped gold nanorods: the effect of silver coating

We report on the identification of surface plasmons in individual gold dumbbell-shaped nanoparticles (AuDBs), as well as AuDBs coated with silver. We use spatially resolved electron energy-loss spectroscopy in a scanning electron microscope, which allows us to map plasmon-energy and intensity spatial distributions. Two dominant plasmon resonances are experimentally resolved in both AuDBs and silver-coated AuDBs. The intensity of these features is peaked either at the tips or at the sides of the nanoparticles. We present boundary element method simulations in good agreement with the experiment, allowing us to elucidate the nature of such modes. While the lower-energy, tip-focused plasmon is of longitudinal character for all dumbbells under consideration, the second side-bound plasmon has a more involved symmetry, starting as a longitudinal quadrupole in homogeneous AuDBs and picking up transversal components when silver coating is added. The longitudinal dipolar mode energy is found to blue-shift upon coating with silver. We find that the substrate produces sizable shifts in the plasmons of silver-coated AuDBs. Our analysis portraits a complex plasmonic scenario in metal nanoparticles coated with silver, including a transition from the original homogeneous gold dumbbell plasmons to the modes of homogeneous silver rods. We believe that these findings can have potential application to plasmon engineering.     

Preparation and Characterization of a Novel Drug Delivery System: Biodegradable Nanoparticles in Thermosensitive Chitosan/Gelatin Blend Hydrogels

A novel injectable in situ gelling drug delivery system (DDS) consisting of biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanoparticles and thermosensitive chitosan/gelatin blend hydrogels was developed for prolonged and sustained controlled drug release. Four different HTCC nanoparticles, prepared based on ionic process of HTCC and oppositely charged molecules such as sodium tripolyphosphate, sodium alginate and carboxymethyl chitosan, were incorporated physically into thermosensitive chitosan/gelatin blend solutions to form the novel DDSs. Resulting DDSs interior morphology was evaluated by scanning electron microscopy. The effect of nanoparticles composition on both the gel process and the gel strength was investigated from which possible hydrogel formation mechanisms were inferred. Finally, bovine serum albumin (BSA), used as a model protein drug, was loaded into four different HTCC nanoparticles to examine and compare the effects of controlled release of these novel DDSs. The results showed that BSA could be sustained and released from these novel DDSs and the release rate was affected by the properties of nanoparticle: the slower BSA release rate was observed from DDS containing nanoparticles with a positive charge than with a negative charge. The described injectable drug delivery systems might have great potential application for local and sustained delivery of protein drugs.     

Effect of molecular weight heterogeneity on drug encapsulation efficiency of gelatin nano-particles

Influence of molecular weight heterogeneity and drug solubility, drug loading and hydrodynamic conditions on drug release kinetics from gelatin nanoparticles were investigated. Also to assess the ability of gelatin nanoparticles as a potential intravascular probe for diagnostic purposes and in improving the biodelivery of cycloheximide (CHX), which is being used as a representative drug. Comparative characterization of 75 Bloom (type B, bovine), 175 and 300 Bloom (type A, porcine) gelatin nanoparticles was done to understand the phase behavior and hydrodynamic properties of gelatin chains and its nanoparticles. Gelatin nanoparticles were prepared by two-step desolvation method. Dynamic light scattering studies were performed to estimate hydrodynamic radii as well as intermolecular interaction. Effects of parameters like pH, temperature and molecular weight on the size and stability of the nanoparticles were studied. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) measurements were done for size and stability analysis. Enhanced visco-elastic properties of nanoparticles were observed as compared to normal solutions of gelatin.     

PVA and BSA stabilized silver nanoparticles based surface-enhanced plasmon resonance probes for protein detection

To perform biosensing using nanoparticles in solution, silver particles were coated with bovine serum albumin (BSA) and polyvinyl alcohol (PVA) as control stabilizer. The plasmon resonance (420 nm) of the silver nanoparticles in solution was shifted slightly to longer wavelength (443 nm) when they were coated with BSA. The biointeractions of these engineered nanoparticles were studied using a mouse model. No significant changes in behavior or toxicity were observed. The nanoparticles were detected in all tissues including the brain. Antibody recognition was monitored via the change in light absorption which accompanied binding, indicating that the particles can be used as a biosensor to gain more insight into cellular mechanisms governing the function of organs in general, and the blood brain barrier (BBB) and brain in particular.     

Targeted Gastrointestinal Delivery of Nutraceuticals with Polysaccharide‐Based Coatings

Oral delivery is one of the facile methods for the administration of active ingredients (AIs) like nutraceuticals and drugs. However, its intrinsic disadvantages include poor absorption and bioavailability, degradation of the AI during transit through the gastrointestinal tract (GIT), and a lack of action specificity. Hence, a delivery system for targeted gastrointestinal delivery of AI using polysaccharide‐based polymers, that are generally recognized as safe and approved for use as a direct food additive, is proposed. In this regard, mucoadhesive chitosan nanoparticles that could adhere to the mucosa of the GIT are fabricated and encapsulated with AI. These particles are subsequently coated with polysaccharides that have different enzymatic susceptibilities, to allow for specific degradation in the small or large intestines. It is observed that the polysaccharide coating efficiently retarded the nonspecific release of the encapsulated agent until it is exposed to its intended environment of release. The cytotoxicity and uptake of chitosan nanoparticles is further evaluated on Caco2 cells. In conclusion, these polysaccharide‐coated nanoparticles can potentially be targeted to different organs in the GIT and to be taken up by the enterocytes for improved oral bioavailability.     

Drug Delivery Vehicles Based on Albumin–Polymer Conjugates

Albumin has been a popular building block to create nanoparticles for drug delivery purposes. The performance of albumin as a drug carrier can be enhanced by combining protein with polymers, which allows the design of carriers to encompass a broader spectrum of drugs while features unique to synthetic polymers such as stimuli‐responsiveness are introduced. Nanoparticles based on polymer–albumin hybrids can be divided into two classes: one that carries album as a bioactive surface coating and the other that uses albumin as biocompatible, although nonbioactive, building block. Nanoparticles with bioactive albumin surface coating can either be prepared by self‐assembly of albumin–polymer conjugates or by postcoating of existing nanoparticles with albumin. Albumin has also been used as building block, either in its native or denatured form. Existing albumin nanoparticles are coated with polymers, which can influence the degradation of albumin or impact on the drug release. Finally, an alternative way of using albumin by denaturing the protein to generate a highly functional chain, which can be modified with polymer, has been presented. These albumin nanoparticles are designed to be extremely versatile so that they can deliver a wide variety of drugs, including traditional hydrophobic drugs, metal‐based drugs and even therapeutic proteins and siRNA.