SEARCH · PubMed Health

Results for “nanoparticles”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources

PubMed2006

Water-induced interactions between carbon nanoparticles.

Molecular dynamics simulations were carried out in order to study the hydration of C60 fullerenes, carbon nanotubes, and graphene sheets in aqueous solution and the nature of water-induced interactions between these carbon nanoparticles. The hydration of these nonpolar carbon nanoparticles does not exhibit classical hydrophobic character due to the high density of surface atoms (carbon) resulting in strong water-surface dispersion interactions. Water was found to wet the nanoparticle surfaces independent of nanoparticle surface curvature, with the decrease in the extent of water-water hydrogen bonding with decreasing surface curvature being offset by stronger water-surface interactions. While all carbon nanoparticles investigated are anticipated to aggregate in water due to strong direct nanoparticle-nanoparticle interactions, the water-induced interactions between nanoparticles were found to be repulsive and, in contrast to the wetting behavior, were observed to exhibit strong dependence on surface curvature. The strength of the water-induced interaction between carbon nanoparticles was found to correlate well with the number of hydration water molecules displaced upon particle aggregation, which, relative to the amount of direct nanoparticle-nanoparticle contact engendered upon aggregation, decreases with decreasing surface curvature.

Carbon↗

PubMed2006

Surface modification of silica nanoparticles to reduce aggregation and nonspecific binding.

In this article, a systematic study of the design and development of surface-modification schemes for silica nanoparticles is presented. The nanoparticle surface design involves an optimum balance of the use of inert and active surface functional groups to achieve minimal nanoparticle aggregation and reduce nanoparticle nonspecific binding. Silica nanoparticles were prepared in a water-in-oil microemulsion and subsequently surface modified via cohydrolysis with tetraethyl orthosilicate (TEOS) and various organosilane reagents. Nanoparticles with different functional groups, including carboxylate, amine, amine/phosphonate, poly(ethylene glycol), octadecyl, and carboxylate/octadecyl groups, were produced. Aggregation studies using SEM, dynamic light scattering, and zeta potential analysis indicate that severe aggregation among amine-modified silica nanoparticles can be reduced by adding inert functional groups, such as methyl phosphonate, to the surface. To determine the effect of various surface-modification schemes on nanoparticle nonspecific binding, the interaction between functionalized silica nanoparticles and a DNA chip was also studied using confocal imaging/fluorescence microscopy. Dye-doped silica nanoparticles functionalized with octadecyl and carboxylate groups showed minimal nonspecific binding. Using these surface-modification schemes, fluorescent dye-doped silica nanoparticles can be more readily conjugated with biomolecules and used as highly fluorescent, sensitive, and reproducible labels in bioanalytical applications.

Coated Materials, Biocompatible↗

PubMed2005

Body distribution and in situ evading of phagocytic uptake by macrophages of long-circulating poly (ethylene glycol) cyanoacrylate-co-n-hexadecyl cyanoacrylate nanoparticles.

AIM: To investigate the body distribution in mice of [14C]-labeled poly methoxyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate (PEG-PHDCA) nanoparticles and in situ evading of phagocytic uptake by mouse peritoneal macrophages. METHODS: PEG-PHDCA copolymers were synthesized by condensation of methoxypolyethylene glycol cyanoacetate with [14C]-hexadecyl-cyanoacetate. [14C]-nanoparticles were prepared using the nanoprecipitation/solvent diffusion method, while fluorescent nanoparticles were prepared by incorporating rhodamine B. In situ phagocytic uptake was evaluated by flow cytometry. Body distribution in mice was evaluated by determining radioactivity in tissues using a scintillation method. RESULTS: Phagocytic uptake by macrophages can be efficiently evaded by fluorescent PEG-PHDCA nanoparticles. After 48 h, 31% of the radioactivity of the stealth [14C]-PEG-PHDCA nanoparticles after iv injection was still found in blood, whereas non-stealth PHDCA nanoparticles were cleaned up from the bloodstream in a short time. The distribution of stealth PEG-PHDCA nanoparticles and non-stealth PHDCA nanoparticals in mice was poor in lung, kidney, and brain, and a little higher in hearts. Lymphatic accumulation was unusually high for both stealth and non-stealth nanoparticles, typical of lymphatic capture. The accumulation of stealth PEG-PHDCA nanoparticles in the spleen was 1.7 times as much as that of non-stealth PHDCA (P< 0.01). But the accumulation of stealth PEG-PHDCA nanoparticles in the liver was 0.8 times as much as that of non-stealth PHDCA (P< 0.05). CONCLUSION: PEGylation leads to long-circulation of nanoparticles in the bloodstream, and splenotropic accumulation opens up the potential for further development of spleen-targeted drug delivery.

Animals↗

PubMed2006

Effects of airway exposure to nanoparticles on lung inflammation induced by bacterial endotoxin in mice.

BACKGROUND: Although adverse health effects of particulate matter with a diameter of < 100 nm (nanoparticles) have been proposed, molecular and/or experimental evidence for their facilitation of lung inflammation in vivo is not fully defined. OBJECTIVE: In the present study we investigated the effects of nanoparticles on lung inflammation related to bacterial endotoxin [lipopolysaccharide (LPS) ] in mice. RESULTS: We intratracheally administered vehicle, two sizes (14 nm, 56 nm) of carbon black nanoparticles (4 mg/kg) , LPS (2.5 mg/kg) , or LPS plus nanoparticles and evaluated parameters for lung inflammation and coagulation. Nanoparticles alone induced slight lung inflammation and significant pulmonary edema compared with vehicle. Fourteen-nanometer nanoparticles intensively aggravated LPS-elicited lung inflammation and pulmonary edema that was concomitant with the enhanced lung expression of interleukin-1beta (IL-1beta) , macrophage inflammatory protein-1alpha (MIP-1alpha) , macrophage chemoattractant protein-1, MIP-2, and keratinocyte chemoattractant in overall trend, whereas 56-nm nanoparticles did not show apparent effects. Immunoreactivity for 8-hydroxyguanosine, a marker for oxidative stress, was more intense in the lungs from the LPS + 14-nm nanoparticle group than in those from the LPS group. Circulatory fibrinogen levels were higher in the LPS + plus 14-nm nanoparticle group than in the LPS group. CONCLUSIONS: Taken together, evidence indicates that nanoparticles can aggravate lung inflammation related to bacterial endotoxin, which is more prominent with smaller particles. The enhancement may be mediated, at least partly, via the increased local expression of proinflammatory cytokines and via the oxidative stress. Furthermore, nanoparticles can promote coagulatory disturbance accompanied by lung inflammation.

Air Pollutants↗

PubMed2006

Distribution of nanoparticles in the see-through medaka (Oryzias latipes).

OBJECTIVE: Because the environmental fate of manufactured nanoparticles is considered an emerging environmental concern, I used water-suspended fluorescent nanoparticles (solid latex solution) to investigate the distribution of nanoparticles in the eggs and bodies of see-through medaka (Oryzias latipes). RESULTS: Particles 39.4-42,000 nm in diameter were adsorbed to the chorion of medaka eggs and accumulated in the oil droplets; 474-nm particles had the highest bioavailability to eggs. Particles 39.4 nm in diameter shifted into the yolk and gallbladder during embryonic development. Adult medaka accumulated 39.4-nm nanoparticles mainly in the gills and intestine when exposed to a 10-mg/L nanoparticle solution. Nanoparticles were also detected in the brain, testis, liver, and blood. Concentrations of nanoparticles in the blood of male and female medaka were 16.5 and 10.5 ng/mg blood protein, respectively. These results suggest that nanoparticles are capable of penetrating the blood-brain barrier and that they eventually reach the brain. Salinity-dependent acute toxicity was observed in medaka eggs exposed for 24 hr to nanoparticles. CONCLUSION: The bioavailability and toxicity of nanoparticles depend on environmental factors and multiple physicochemical properties. Further studies on the toxic effects of nanoparticles used in commercial products and their environmental relevance, are necessary to define the risks and benefit of nanomaterial applications.

Adsorption↗

PubMed2005

[PEI-PMMA cationic nanoparticles as carriers for gene transfer].

AIM: To investigate the properties of cationic nanoparticles composed of poly (ethyleneimine)-g-poly (methyl methacrylate) (PEI-PMMA) as gene delivery carriers and explore the mechanism of PEI-PMMA nanoparticles mediated gene transfer. METHODS: PEI-PMMA nanoparticles were synthesized by free radical polymerization. The morphology of nanoparticles was observed by scanning electron microscopy. The particle size and zeta potential were measured by zeta sizer. The complex between pGL3 plasmid and nanoparticles was analyzed by gel electrophoresis; and PEI-PMMA nanoparticles mediated gene transfer into HeLa cells was observed by confocal laser scanning microscopy. RESULTS: PEI-PMMA nanoparticles are spherical shape and monodispersity. The particle size and zeta potential are 172 nm and +50.3 mV, respectively. When pGL3 plasmid complexed with nanoparticles at N/P ratio of 5: 1 and 20: 1, the particle size of pGL3/nanoparticle complex are 133 and 139 nm and zeta potential is + 21.4 and + 33.7 mV, respectively. pGL3 plasmid complexed with nanoparticles completely at N/P ratio of 5: 1. PEI-PMMA nanoparticles can deliver pGL3 plasmid into HeLa cells by endocytosis and release pGL3 into the cytosol. CONCLUSION: PEI-PMMA nanoparticles effectively transferred DNA to target cells and it is a promising non-viral carrier for gene delivery.

DNA↗

PubMed2004

Mechanistic study of the uptake of wheat germ agglutinin-conjugated PLGA nanoparticles by A549 cells.

The purpose of this study was to evaluate the extent and mechanism of uptake of wheat germ agglutinin-conjugated PLGA nanoparticles by A549 cells. PLGA nanoparticles of 150 nm were prepared by a solvent diffusion method and covalently conjugated to FITC-WGA (fWGA) or FITC-bovine serum albumin (fBSA) by a two-step carbodiimide method. Uptake of fWGA-PLGA and fBSA-PLGA nanoparticles by confluent A549 cells was quantified by fluorometry. A549 cellular uptake of fWGA-PLGA nanoparticles at 2 h, 37 degrees C was 5.02-fold that of fBSA-PLGA nanoparticles at a loading concentration of 2.65 mg/mL. The difference in uptake between the two types of nanoparticles was increased to 7.84-fold at a higher loading concentration of 5.3 mg/mL, but was reduced to 2.07-fold by lowering the uptake temperature to 4 degrees C. Coincubation with 5 mg/mL of unlabeled WGA negated the differential uptake of fWGA-PLGA nanoparticles at 4 degrees C, suggesting that the nanoparticles interacted with a specific WGA-binding receptor on the cell membrane. Internalization of the fWGA-PLGA nanoparticles by the A549 cells was confirmed by confocal microscopy. Filipin (1 microg/mL), a known inhibitor of caveolae, reduced the 1-h uptake of the nanoparticles by 75%. Surface modification of PLGA nanoparticles with WGA significantly enhanced its endocytosis by A549 cells by a receptor-mediated, caveola-dependent pathway.

Biomechanical Phenomena↗

PubMed2004

Bioadhesive, non-drug-loaded nanoparticles as modulators of candidal adherence to buccal epithelial cells: a potentially novel prophylaxis for candidosis.

Adherence of microorganisms, such as Candida albicans, represents the initial step in the establishment of infection and, accordingly, modification of this step represents a method by which the incidence of infection may be reduced. Therefore, this study uniquely examined the effects of polymeric nanoparticles on the adherence of blastospores of C. albicans to human buccal epithelial cells (BEC) in vitro. Poly(propylcyanoacrylate) nanoparticles were produced by emulsion polymerisation using a range of anionic, cationic and non-ionic surfactants, their particle size and zeta potential characterised and incubated with stationary phase blastospores of C. albicans for a defined period. Following this, the surface properties and size of blastospores with adsorbed nanoparticles were characterised. phosphate buffered saline-treated and nanoparticle-treated blastospores were incubated with human BEC for 2 h, following which the number of adherent blastospores was enumerated by light microscopy. The size and zeta potential of the nanoparticles were dependent on the surfactant employed in the manufacture process. Following nanoparticle adsorption, alteration of the zeta potential and an increase in the diameter of blastospores were observed. However, as this increase in diameter was indirectly related to the size of the nanoparticles, this may indicate a preference for the adsorption of smaller particles. In addition, following nanoparticle adsorption, the cell surface hydrophobicity (CSH) of C. albicans blastospores was increased and, importantly, the subsequent adherence to BEC in vitro was reduced. Most notably, the adherence of blastospores that had been treated with nanoparticles (stabilised with docusate sodium) was circa 73% lower than that of untreated blastospores. A moderate correlation between increased CSH and reduced adherence and a low correlation between blastospore zeta potential and adherence were observed, inferring that other mechanisms, most likely stearic hindrance, are responsible for the antiadherent properties of adsorbed nanoparticles. In light of their ability to reduce candidal adherence to BEC, it is suggested that polymeric nanoparticles may be useful in the prophylaxis of candidosis of the oral cavity.

Animals↗

PubMed2006

Dual mode bioreactions on polymer nanoparticles covered with phosphorylcholine group.

We investigated the preparation of polymer nanoparticles covered with phosphorylcholine (PC) groups and the immobilization of proteins in order to observe dual mode bioreactions on the nanoparticles. For the surface modification on the nanoparticles, a water-soluble amphiphilic phospholipid polymer with PC groups as a hydrophilic moiety was synthesized. In this polymer, an active ester group, which can immobilize proteins, was introduced. Using the phospholipid polymer as a solubilizer, poly(L-lactic acid) nanoparticles were prepared from its methylene chloride solution in an aqueous medium by the solvent evaporation method. The diameter of the nanoparticles was ca. 200 nm and the surface was covered with the PC groups and active ester groups. Proteins could immobilize on the nanoparticles under mild conditions by the reaction between the active ester group and amino group in the proteins. Both an antibody and enzyme were immobilized on the nanoparticles and bioreactions such as the antigen/antibody reaction and enzymatic reaction were observed. When an antigen was added to the suspension of the nanoparticles, aggregation of the nanoparticles occurred and then they precipitated. Also, the enzymatic reaction proceeded well when the enzyme substrate was added to the suspension. Based on these results, we provided polymer nanoparticles functionalized with both the antibody and enzyme, and the dual mode bioreactions could occur. We concluded that the novel polymer nanoparticles could be used for nano-/micro-scaled diagnostic and medical treatment systems.

Antibodies, Monoclonal↗

PubMed2004

Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice.

High molecular weight (Mw) chitosan (CS) solutions have already been proposed as vehicles for nasal immunization. The aim of the present work was to investigate the potential utility of low Mw CS in the form of nanoparticles as new long-term nasal vaccine delivery vehicles. For this purpose, CS of low Mws (23 and 38 kDa) was obtained previously by a depolymerization process of the commercially available CS (70 kDa). Tetanus toxoid (TT), used as a model antigen, was entrapped within CS nanoparticles by an ionic cross-linking technique. TT-loaded nanoparticles were first characterized for their size, electrical charge, loading efficiency and in vitro release of antigenically active toxoid. The nanoparticles were then administered intranasally to conscious mice in order to study their feasibility as vaccine carriers. CS nanoparticles were also labeled with FITC-BSA and their interaction with the rat nasal mucosa examined by confocal laser scanning microcopy (CLSM). Irrespective of the CS Mw, the nanoparticles were in the 350 nm size range, and exhibited a positive electrical charge (+40 mV) and associated TT quite efficiently (loading efficiency: 50-60%). In vitro release studies showed an initial burst followed by an extended release of antigenically active toxoid. Following intranasal administration, TT-loaded nanoparticles elicited an increasing and long-lasting humoral immune response (IgG concentrations) as compared to the fluid vaccine. Similarly, the mucosal response (IgA levels) at 6 months post-administration of TT-loaded CS nanoparticles was significantly higher than that obtained for the fluid vaccine. The CLSM images indicated that CS nanoparticles can cross the nasal epithelia and, hence, transport the associated antigen. Interestingly, the ability of these nanoparticles to provide improved access to the associated antigen to the immune system was not significantly affected by the CS Mw. Indeed, high and long-lasting responses could be obtained using low Mw CS molecules. Furthermore, the response was not influenced by the CS dose (70-200 microg), achieving a significant response for a very low CS dose. In conclusion, nanoparticles made of low Mw CS are promising carriers for nasal vaccine delivery.

Administration, Intranasal↗

PubMed2004

pH-sensitive nanoparticles for improving the oral bioavailability of cyclosporine A.

The purpose of this work was to improve the oral bioavailability of cyclosporine A (CyA) by preparation the CyA-pH sensitive nanoparticles. The CyA-pH sensitive nanoparticles were prepared by using poly(methacrylic acid and methacrylate) copolymer. The characterization and the dispersion state of CyA at the surface or inside the polymeric matrices of the nanoparticles were investigated. The in vitro release studies were conducted by ultracentrifuge method. The bioavailability of CyA from nanoparticles and Neoral microemulsion was assessed in Sprague-Dawley (SD) rats at a dose of 15 mg/kg. The particle size of the nanoparticles was within the range from 37.4 +/- 5.6 to 106.7 +/- 14.8 nm. The drug entrapped efficiency was very high (from 90.9 to 99.9%) and in all cases the drug was amorphous or molecularly dispersed within the nanoparticles polymeric matrices. In vitro release experiments revealed that the nanoparticles exhibited perfect pH-dependant release profiles. The relative bioavailability of CyA was markedly increased by 32.5% for CyA-S100 nanoparticles (P < 0.05), and by 15.2% and 13.6% for CyA-L100-55 and CyA-L100 nanoparticles respectively, while it was decreased by 5.2% from CyA-E100 nanoparticles when compared with the Neoral microemulsion. With these results, the potential of pH-sensitive nanoparticles for the oral delivery of CyA was confirmed.

Administration, Oral↗

PubMed2005

A novel method for the preparation of silver chloride nanoparticles starting from their solid powder using microemulsions.

A novel method of preparing AgCl nanoparticles by mixing AgCl powder and a microemulsion consisting of dioctyldimethylammonium chloride/n-decanol/water/isooctane is introduced. This new method was discovered during the preparation of AgCl nanoparticles in single microemulsions by direct reaction with the dioctyldimethylammonium chloride surfactant counterion. The effect of the following variables on the concentration of the colloidal AgCl nanoparticles (the nanoparticle uptake) and the particle size were studied: (1) operating variables, including mixing and temperature; and (2) microemulsion variables, including surfactant and cosurfactant concentration, and water to surfactant mole ratio. Manipulating these variables provides an insight into the role of the surfactant surface layer rigidity on the phenomenon. The results were explained by the effect of these variables on reaction rates and the colloidal nanoparticle stability. Mixing had a significant effect on the nanoparticle uptake. At 300 rpm an equilibrium AgCl nanoparticle uptake was achieved in about 1 h, while without mixing only 5% of the equilibrium value was reached even after 24 h. An optimum temperature was found for which a maximum nanoparticle uptake was obtained. At higher temperatures, the nanoparticle uptake declined. The nanoparticle uptake increased linearly with the surfactant concentration, and the particle size increased as well. A monotonic decrease in the nanoparticle uptake accompanied by an increase in the particle size was observed when increasing n-decanol concentration or the water to surfactant mole ratio.

Alkanes↗

PubMed2006

Experimental investigation of nanoparticle dispersion by beads milling with centrifugal bead separation.

A new type of beads mill for dispersing nanoparticles into liquids has been developed. The bead mill utilizes centrifugation to separate beads from nanoparticle suspensions and allows for the use of small sized beads (i.e. 15-30 microm in diameter). The performance of the beads mill in dispersing a suspension of titanium dioxide nanoparticle with 15 nm primary particles was evaluated experimentally. Dynamic light scattering was used to measure titania particle size distributions over time during the milling process, and bead sizes in the 15-100 microm range were used. It was found that larger beads (50-100 microm) were not capable of fully dispersing nanoparticles, and particles reagglomerated after long milling times. Smaller beads (15-30 microm) were capable of dispersing nanoparticles, and a sharp peak around 15 nm in the titania size distribution was visible when smaller beads were used. Because nanoparticle collisions with smaller beads have lower impact energy, it was found by X-ray diffraction and transmission electron microscopy that changes in nanoparticle crystallinity and morphology are minimized when smaller beads are used. Furthermore, inductively-coupled plasma spectroscopy was used to determine the level of bead contamination in the nanoparticle suspension during milling, and it was found that smaller beads are less likely to fragment and contaminate nanoparticle suspensions. The new type of beads mill is capable of effectively dispersing nanoparticle suspensions and will be extremely useful in future nanoparticle research.

Microscopy, Electron, Transmission↗

PubMed2006

N-acetyl histidine-conjugated glycol chitosan self-assembled nanoparticles for intracytoplasmic delivery of drugs: endocytosis, exocytosis and drug release.

Nano-sized vesicular systems (nanoparticles), ranging from 10 nm to 1000 nm in size, have potential applications as drug delivery systems. Successful clinical applications require the efficient intracellular delivery of drug-loaded nanoparticles. Here we describe N-acetyl histidine-conjugated glycol chitosan (NAcHis-GC) self-assembled nanoparticles as a promising system for intracytoplasmic delivery of drugs. Because N-acetyl histidine (NAcHis) is hydrophobic at neutral pH, the conjugates formed self-assembled nanoparticles with mean diameters of 150-250 nm. In slightly acidic environments, such as those in endosomes, the nanoparticles were disassembled due to breakdown of the hydrophilic/hydrophobic balance by the protonation of the imidazole group of NAcHis. Cellular internalization and drug release of the pH-sensitive self-assembled nanoparticles were investigated by flow cytometry and confocal microscopy. NAcHis-GC nanoparticles internalized by adsorptive endocytosis were exocytosed or localized in endosomes. The amount of exocytosed nanoparticles was dependent on the pre-incubation time prior to removal of free nanoparticles from the culture media. Flow cytometry and confocal microscopy showed that NAcHis-GC nanoparticles released drugs into the cytosol and cell cycle analysis demonstrated that paclitaxel-incorporated NAcHis-GC nanoparticles were effective in inducing arrest of cell growth.

Antineoplastic Agents, Phytogenic↗

PubMed2001

PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats.

The aim of the present work was to assess the merits of PEGylated poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles as protein and peptide drugs (PPD) carriers. PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles or long-circulating nanoparticles, was synthesized with methoxypolyethyleneglycol (MePEG) and PLGA. The structure of PEG-PLGA was confirmed with (1)H NMR and Fourier transform infrared (FTIR) spectrum, and molecular weight was determined by gel permeation chromatography (GPC). Bovine serum albumin (BSA), chosen as model protein, was encapsulated within the stealth nanoparticles with the double emulsion method. The particles were characterized in terms of size, zeta potential and in vitro release of the protein. The biological fate of the BSA-loaded nanoparticles following intravenous administration was determined over 24 h in rats. The experimental results showed that PEG-PLGA could be obtained by ring-opening polymerization of lactide and glycolide in the presence of MePEG. (1)H NMR and FTIR spectrum were consistent with the structure of PEG-PLGA copolymer. Molecular weight determined by GPC was 50800. The stealth nanoparticles loading BSA could be prepared by the double emulsion technique. The entrapment efficiency was 48.6%, particle size about 200 nm and zeta potential -16.1 mV. BSA release from the stealth nanoparticles showed an initial burst release and then sustained release. PEG-PLGA nanoparticles could extend half-life of BSA from 13.6 min of loaded in PLGA nanoparticles to 4.5 h and obviously change the protein biodistribution in rats compared with that of PLGA nanoparticles. Thus, PEG-PLGA nanoparticles could be an effective carrier for PPD delivery.

Animals↗

PubMed2002

Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake.

Polyvinyl alcohol (PVA) is the most commonly used emulsifier in the formulation of poly lactide and poly (D,L-lactide-co-glycolide) (PLGA) polymeric nanoparticles. A fraction of PVA remains associated with the nanoparticles despite repeated washing because PVA forms an interconnected network with the polymer at the interface. The objective of this study was to determine the parameters that influence the amount of residual PVA associated with PLGA nanoparticles and its effect on the physical properties and cellular uptake of nanoparticles. Nanoparticles were formulated by a multiple emulsion-solvent evaporation technique using bovine serum albumin (BSA) as a model protein. The parameters that affected the amount of residual PVA include the concentration of PVA and the type of organic solvent used in the emulsion. The residual PVA, in turn, influenced different pharmaceutical properties of nanoparticles such as particle size, zeta potential, polydispersity index, surface hydrophobicity, protein loading and also slightly influenced the in vitro release of the encapsulated protein. Importantly, nanoparticles with higher amount of residual PVA had relatively lower cellular uptake despite their smaller particle size. It is proposed that the lower intracellular uptake of nanoparticles with higher amount of residual PVA could be related to the higher hydrophilicity of the nanoparticle surface. In conclusion, the residual PVA associated with nanoparticles is an important formulation parameter that can be used to modulate the pharmaceutical properties of PLGA nanoparticles.

Biocompatible Materials↗

PubMed2000

Studies on the cyclosporin A loaded stearic acid nanoparticles.

Stearic acid nanoparticles were prepared in this study by melt-homogenization to investigate the possibility of them as a new kind of drug carrier system. Some physicochemical properties of stearic acid nanoparticles were studied and morphology examined by transmission electron microscope. Cyclosporin A as a model drug was then encapsulated into stearic acid nanoparticles. Following the establishment of high performance liquid chromatography assay for cyclosporin A analysis in stearic acid nanoparticles or blood samples, the encapsulation ratio of cyclosporin A to stearic acid nanoparticles was estimated and pharmacokinetics as well as bioavailability of cyclosporin A stearic acid nanoparticles after oral administration to Wistar rats were studied, using the Sandimmun Neoral(R) (an available microemulsion system of cyclosporin A) as a reference. The mean diameter of cyclosporin A stearic acid nanoparticles was 316.1 nm, while the encapsulation ratio of cyclosporin A to stearic acid nanoparticles reached to 88.36%. It was demonstrated by IR spectra and differential scanning calorimetry that there was no chemical reaction occurred between the cyclosporin A and stearic acid. The relative bioavailability of cyclosporin A stearic acid nanoparticles over reference was nearly 80%, and the time to reach maximum concentration (T(max)) of cyclosporin A after oral administration of cyclosporin A stearic acid nanoparticles was delayed significantly than the reference, suggesting an obvious sustained release effect. The stearic acid nanoparticles might be a very potential drug carrier.

Administration, Oral↗

PubMed2003

Influence of formulation parameters on gadolinium entrapment and tumor cell uptake using folate-coated nanoparticles.

Emulsifying wax and polyoxyl 2 stearyl ether (Brij 72) nanoparticles (2 mg/ml) containing high concentrations of gadolinium hexanedione (GdH) (0-3 mg) have been engineered from oil-in-water microemulsion templates. Solid nanoparticles were cured by cooling warm microemulsion templates (prepared at 55 degrees C) to room temperature in one vessel. Nanoparticles were characterized by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS) and gel permeation chromatography (GPC). To obtain folate-coated nanoparticles, a folate ligand was added to either the microemulsion templates or nanoparticle suspensions at 25 degrees C. Since the concentration of Gd in the tumor is critical to the success of Gd-neutron capture therapy (NCT), the effects of various formulation factors on GdH entrapment in nanoparticles as well as tumor-targeting were studied. GdH entrapment in nanoparticles was affected mostly by the method of GdH incorporation and surfactant concentration used in preparing the microemulsion templates. Cell uptake studies were carried out in KB cells (human nasopharyngeal epidermal carcinoma cell line). The method of adding folate ligand to the formulations did not significantly affect nanoparticle cell uptake (P>0.11; t-test). However, the concentration of folate ligand added to nanoparticles had the greatest influence on nanoparticle uptake (P<0.01; t-test). The results showed that GdH entrapment and cell uptake were optimized and suggested that engineered folate-coated nanoparticles may serve as effective carrier systems for Gd-NCT of tumors.

Chemistry, Pharmaceutical↗