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Retinol-encapsulated low molecular water-soluble chitosan nanoparticles.

This aim of this study was to encapsulate retinol into chitosan nanoparticles and reconstitute it into aqueous solution. Retinol-encapsulated chitosan nanoparticles were prepared for application of cosmetic and pharmaceutical applications. Retinol-encapsulated chitosan nanoparticle has a spherical shape and its particle sizes were around 50-200 nm according to the drug contents. Particle size was increased according to the increase of drug contents. Solubility of retinol is able to increase by encapsulation into chitosan nanoparticles more than 1600-fold. It was suggested that retinol was encapsulated into chitosan nanoparticles by ion complex as a result of FT-IR spectra. Specific peak of chitosan at 1590 cm(-1) was divided to semi-doublet due to the electrostatic interaction between amine group of chitosan and hydroxyl group of retinol. At (1)H NMR spectra, specific peaks of retinol disappeared when retinol-encapsulated chitosan nanoparticles were reconstituted into D(2)O while specific peaks both of retinol and chitosan appeared at D(2)O/DMSO (1/4, v/v) mixture. XRD patterns also showed that crystal peaks of retinol were disappeared by encapsulation into chitosan nanoparticles. Retinol-encapsulated nanoparticles were completely reconstituted into aqueous solution as same as original aqueous solution and zeta potential of reconstituted chitosan nanoparticles was similar to their original solution. At HPLC study, retinol was stably and efficiently encapsulated into chitosan nanoparticles.

Chitosan↗

Intracellular photodynamic therapy with photosensitizer-nanoparticle conjugates: cancer therapy using a 'Trojan horse'.

Phthalocyanine-nanoparticle conjugates have been designed and synthesised for the delivery of hydrophobic photosensitizers for photodynamic therapy (PDT) of cancer. The phthalocyanine photosensitizer stabilized gold nanoparticles have an average diameter of 2-4 nm. The synthetic strategy interdigitates a phase transfer reagent between phthalocyanine molecules on the particle surface that solubilises the hydrophobic photosensitizer in polar solvents enabling delivery of the nanoparticle conjugates to cells. The phthalocyanine is present in the monomeric form on the nanoparticle surface, absorbs radiation maximally at 695 nm and catalytically produces the cytotoxic species singlet oxygen with high efficiency. These properties suggest that the phthalocyanine-nanoparticle conjugates are ideally suited for PDT. In a process that can be considered as cancer therapy using a 'Trojan horse', when the nanoparticle conjugates are incubated with HeLa cells (a cervical cancer cell line), they are taken up thus delivering the phthalocyanine photosensitizer directly into the cell interior. Irradiation of the nanoparticle conjugates within the HeLa cells induced substantial cell mortality through the photodynamic production of singlet oxygen. The PDT efficiency of the nanoparticle conjugates, determined using colorimetric assay, was twice that obtained using the free phthalocyanine derivative. Following PDT with the nanoparticle conjugates, morphological changes to the HeLa cellular structure were indicative of cell mortality via apoptosis. Further evidence of apoptosis was provided through the bioluminescent assay detection of caspase 3/7. Our results suggest that gold nanoparticle conjugates are an excellent vehicle for the delivery of surface bound hydrophobic photosensitizers for efficacious photodynamic therapy of cultured tumour cells.

Apoptosis↗

[Photosensitizer nanoparticles photodynamic therapy on LOVO human colon cancer xenografts in athymic mice].

OBJECTIVE: To evaluate the inhibitory of profrin II nanoparticles photodynamic therapy on Lovo human colon cancer xenografts in athymic mice. METHODS: Profrin II nanoparticles were obtained from hypersound emulsification method. LOVO human colon cancer xenograft were established in athymic mice. Athymic mice were divided into four groups:normal control group, profrin II nanoparticles control group, profrin II PDT group and profrin II nanoparticles PDT group. The animals bearing xenografts were treated 30 mg/kg body weight profrin II nanoparticles and 3 h later were irradiated with 9 J/cm(2) light from a diode laser. After Profrin II nanoparticles PDT, the anti-tumor effect was assessed by measuring tumor volume over a 3-4 weeks period, the morphologic changes were observed by microscopy and microscopy via the histological examination. RESULTS: Compared with the control groups, profrin II nanoparticles control group, profrin II PDT group and profrin II nanoparticles-PDT treated tumors had regressed significantly in earlier period with the inhibiting rate being 87.9% (P<0.05), 87.5% (P<0.05) and 56.0% respectively (P<0.05). In the later period post-PDT, tumors growth resumed with a slower rate. Profrin II nanoparticles-PDT prolonged the survival time in the treated group with (38.0+/-6.0) days (P<0.05). Extensive damage to tumor tissue was found in the earlier period (7d) post-PDT, whereas in the later period (21d) post-PDT, islands of vital-looking tumor cells were observed around the damaged tissue. CONCLUSION: Profrin II nanoparticles-PDT results in inhibition Lovo colon carcinoma growth in post-PDT earlier period in vivo, and can prolong the survival time of nude mice bearing xenografts significantly, whereas profrin II-PDT could not inhibit the growth of colon tumor completely.

Animals↗

[Preparation of magnetic solid liposome nanoparticles of paclitaxel].

AIM: To study a new way to prepare high-dosage paclitaxel entrapped magnetic targeted nanoparticles and evaluate its quality. METHODS: Fe3O4 nanoparticles are prepared by co-depositing, at the same time ultrasonic is used to decrease soft agglomerate of nanoparticles and increase disperse level of it. The property of nanoparticles surface is improved to make the integrating of liposome and nanoparticle to be tighter. At last, paclitaxel entrapped magnetic solid liposome nanoparticles have been prepared by microemulsion-curing under low-temperature. The loading efficiency and encapsulating rate were determined by reverse-phase high-perfomance chromatography. RESULTS: The nanoparticles have spherical shape. Diameter of nanoparticle ranged from 150 nm to 170 nm. 98.29% of the drug is entrapped in the particle. CONCLUSION: Magnetic susceptibility of nanoparticles is high, and the nanoparticles meet with the demand of targeted delivery system.

Antineoplastic Agents, Phytogenic↗

Transport of surface-modified nanoparticles through cell monolayers.

We synthesized three peptides, a D-polyarginyl peptide (r8(FITC)), a Tat peptide (Tat(FITC)), and a control peptide (Cp(FITC)) and attached each to amino-CLIO, a nanoparticle 30 nm in diameter. We then examined the effective permeability, Peff, of all six materials through CaCo-2 monolayers. The transport of peptide-nanoparticles was characterized by a lag phase (0-8 h) and a steady-state phase (9-27 h). The steady-state Peff values for peptides were in the order r8(FITC)>Tat(FITC)=Cp(FITC). When r8(FITC) and Tat(FITC) peptides were attached to the nanoparticle, they conferred their propensity to traverse cell monolayers onto the nanoparticle, whereas Cp(FITC) did not. Thus, when the r8(FITC) peptide was attached to the amino-CLIO nanoparticle, the resulting peptide-nanoparticle had a Peff similar to that of this poly-D-arginyl peptide alone. The Peff of r8(FITC)-CLIO (MW approximately 1000 kDa) was similar to that of mannitol (MW=182 Da), a poorly transported reference substance, with a far lower molecular weight. These results are the first to indicate that the modification of nanoparticles by attachment of membrane-translocating sequence-based peptides can alter nanoparticle transport through monolayers. This suggests that the surface modification of nanoparticles might be a general strategy for enhancing the permeability of drugs and that high-permeability nanoparticle-based therapeutics can be useful in selected pharmaceutical applications.

Biological Transport↗

A general method for the synthesis of nanostructured large-surface-area materials through the self-assembly of functionalized nanoparticles.

A general synthetic method for the preparation of nanostructured materials with large surface area was developed by using nanoparticle building blocks. The preparation route involves the self-assembly of functionalized nanoparticles in a liquid-crystal phase. These nanoparticles are functionalized by using difunctional amino acid species to provide suitable interactions with the template. Optimum interactions for self-assembly of the nanoparticles in the liquid-crystal phase were achieved with one -NH2 group anchored to the nanoparticle surface per 25 A(2). To maximize the surface area of these materials, the wall thicknesses are adjusted so that they are composed of a monolayer of nanoparticles. To form such materials, numerous parameters have to be controlled such as the relative volume fraction of the nanoparticles and the template and size matching between the hydrophilic component of the copolymer and nanoparticles. The surface functionalization renders our synthetic route independent of the nanoparticles and allows us to prepare a variety of nanostructured composite materials that consist of a juxtaposition of different discrete oxide nanoparticles. Examples of such materials include CeO2, ZrO2, and CeO2-Al(OH)3 composites.

Aluminum Hydroxide↗

Nanoparticles for bioanalysis.

This review covers the emerging field of nanobiotechnology, in which nanoparticles are applied to the analysis of biomolecules. Nanoparticles can be used in a variety of bioanalytical formats, and this review discusses four classes of use. First, nanoparticles as quantitation tags, such as the optical detection of quantum dots and the electrochemical detection of metallic nanoparticles. Second, encoded nanoparticles as substrates for multiplexed bioassays, such as striped metallic nanoparticles. Third, nanoparticles that leverage signal transduction, for example in colloidal gold-based aggregation assays. Fourth, functional nanoparticles that exploit specific physical or chemical properties of nanoparticles to carry out novel functions, such as the catalysis of a biological reaction. In addition, the review discusses the next generation of nanoparticles that will be utilized in the life sciences, such as nanodots and carbon nanotubes.

Biosensing Techniques↗

Hydrodynamic fragmentation of nanoparticle aggregates at orthokinetic coagulation.

Hydrodynamic forces on a doublet of large particles or aggregates during sedimentation cause the non-inertial fragmentation of the doublet, if the doublet Reynolds number and Stokes number are small. In lio-dispersed systems, this non-inertial fragmentation is known to promote the wet classification of large particles whereas the small particles are aggregated (in the secondary minimum) and hence cannot be separated despite the electrostatic repulsion. In aero-dispersed systems with negligible electrostatic repulsion, it is possible to have a narrower separation between two interacting particles so that the attractive surface forces such as van der Waals force could increase in orders of magnitude. As a result, the doublet fragmentation by the aerodynamic detaching force becomes very difficult or even impossible in sedimentation at a small Re. However, this study shows that, when extending above analysis for the interacting fractal aggregates of nanoparticles in a suspension, it is still possible to have aggregate (doublet of two nano-aggregates) fragmentation by the aerodynamic detaching force because the surface forces for nanoparticle contact between two aggregates may be in orders of magnitude smaller than that for micron-sized particles. Even with multiple contacts between two interacting nanoparticle aggregates, this prediction of aggregate fragmentation may still be valid because the contacts may break step by step due to the aggregate rolling along each other caused by a short-range aerodynamic interaction during their differential settling. The aerodynamics of aero-dispersed nanoparticle aggregates is analogous to the hydrodynamics of lio-dispersed solid particles. Therefore the hydrodynamic fragmentation model may be used to partially interpret the stability of nanoparticle fluidization process. Our model indicates that, without continued doublet fragmentation of nano-aggregates, the fluidized nanoparticle suspension would be de-fluidized within minutes via the cascading aggregation. However, the experimental evidence of a sustained operation of fluidization of nanoparticle aggregates over a very long time period without changing the size of nanoparticle aggregates indicates that there is a dynamic balance between the aggregation and fragmentation of nano-aggregates in nanoparticle fluidization. The prediction of critical size of nanoparticle aggregates caused by fragmentation in stabilized fluidization agrees with our in situ measurements.

Kinetics↗

Poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer.

This study was carried out to evaluate and compare the biodistribution profile of tamoxifen when administered intravenously (i.v.) as a simple solution or when encapsulated in polymeric nanoparticulate formulations, with or without surface-stabilizing agents. Tamoxifen-loaded, poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles were prepared by solvent displacement process that allowed in situ surface modification via physical adsorption of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock polymeric stabilizer (Pluronic). The nanoparticles were characterized for particle size and surface charge. Presence of PEO chains on nanoparticle surface was ascertained by electron spectroscopy for chemical analysis (ESCA). In vivo biodistribution studies were carried out in Nu/Nu athymic mice bearing a human breast carcinoma xenograft, MDA-MB-231 using tritiated [(3)H]-tamoxifen as radio-marker for quantification. PEO-PCL nanoparticles with an average diameter of 150-250 nm, having a smooth spherical shape, and a positive surface charge were obtained with the formulation procedure. About 90% drug encapsulation efficiency was achieved when tamoxifen was loaded at 10% by weight of the polymer. Aqueous wettability, suspendability, and ESCA results showed surface hydrophilization of the PCL nanoparticles by the Pluronics. The primary site of accumulation for the drug-loaded nanoparticles after i.v. administration was the liver, though up to 26% of the total activity could be recovered in tumor at 6h post-injection for PEO-modified nanoparticles. PEO-PCL nanoparticles exhibited significantly increased level of accumulation of the drug within tumor with time as well as extended their presence in the systemic circulation than the controls (unmodified nanoparticles or the solution form). Pluronic surfactants (F-68 and F-108) presented simple means for efficient surface modification and stabilization of PCL nanoparticles to achieve preferential tumor-targeting and a circulating drug reservoir for tamoxifen.

Animals↗

Preparation and characterization of mucoadhesive polymer-coated nanoparticles.

The transmucosal routes such as pulmonary, nasal and oral routes are most important and common routes for drug delivering to the body. However, peptide and protein drugs are degraded before they reach the blood stream and cannot cross the mucosal barriers. The mucoadhesive polymer-coated nanoparticles colloidal carriers can solve these problems. In the present investigation, mucoadhesive polymer-coated nanoparticles were prepared by emulsion polymerization process. A detailed preparation procedure of the mucoadhesive polymer-coated nanoparticles was provided. The parameters such as portion of the mucoadhesive polymers and concentration of the radical initiator were investigated. The resulting chitosan-coated nanoparticles colloids possessed positive surface charge, while poly(acrylic acid)-coated nanoparticles colloids and carbopol-coated nanoparticles colloids had negative surface charge. These nanoparticles were suitable for carrying hydrophilic protein or peptide drugs. Chitosan-coated nanoparticles were stable when pH value below 11, while poly(acrylic acid)-coated nanoparticles and carbopol-coated nanoparticles were stable under physiological pH conditions. Therefore, they are promising for transmucosal drug delivery.

Acrylic Resins↗

The feasibility of inert colloidal processing of silicon nanoparticles.

Silicon nanoparticles have important applications, including nonvolatile floating-gate memory devices. To prevent device performance variations, particle size and oxide thicknesses need to be controlled with a high degree of precision. Additionally, producing well-ordered, two-dimensional arrays of nanoparticles may require the exploitation of self-assembly techniques and colloidal forces, which in turn requires that silicon nanoparticles first come into contact with liquids. Until recently, aerosol silicon nanoparticle collection into liquid was assumed to be an inert process. Once formed, the silicon nanoparticle colloid was assumed to be inert. In fact, silicon nanoparticles produced in the aerosol phase by dilute silane pyrolysis and size classified with a differential mobility analyzer undergo a size reduction upon collection in ethylene glycol, water, and ethanol. Unclassified polydisperse silicon aerosol nanoparticles with an average diameter of 11 nm become monodisperse when collected in a colloid and have a final particle diameter of 2-5 nm. Further evidence suggests that silicon nanoparticles collected in ethanol react with the ethanol to produce tetraalkylorthosilicate-like species. Collections of aerosol silicon nanoparticles in degassed water do not show measurable differences between the aerosol and colloidal size distributions. This reduced reactivity to the solvent indicates that the presence of dissolved oxygen in the solvent may be responsible for the reactivity between the silicon nanoparticles and the solvent.

Journal Article↗

Albumin nanoparticles improved the stability, nuclear accumulation and anticytomegaloviral activity of a phosphodiester oligonucleotide.

The goal of this study was to evaluate the potential of albumin nanoparticles as a delivery system for antisense oligonucleotides. Nanoparticles were prepared by a coacervation process and cross-linkage with glutaraldehyde. Phosphodiester (PO) and phosphorotioate (PS) oligonucleotides were either adsorbed on the surface of nanoparticles (PO-NPA and PS-NPA) or incorporated in the nanoparticle matrix (PO-NPB and PS-NPB). When PO-loaded nanoparticles were incubated with phosphodiesterase, only NPB was able to keep the oligonucleotide hybridization capability for at least 60 min. The antiviral activity was evaluated in MRC-5 fibroblasts infected with human cytomegalovirus at a MOI of 0.0035. Both PO nanoparticle formulations significantly increased the antiviral activity of free PO (P<0.001) and NPB showed slightly higher efficacies than NPA (P<0.05). On the other hand, PS exhibited significant higher activity than free PO (P<0.001), however, no significant differences were found between PS-nanoparticle and PO-nanoparticle formulations. These findings were well correlated with the intracellular distribution observed for fluorescent oligonucleotide-loaded albumin nanoparticles. Even these carriers delayed and decreased the uptake of PO by MRC-5 cells, they finally induced a diffused cytoplasmic distribution and major nuclear accumulation. In summary, albumin nanoparticles partially protected a PO against enzymatic degradation and improved their presence in the nucleus and thus, increased its efficiency.

Albumins↗

pH-sensitivity and pH-dependent interior structural change of self-assembled hydrogel nanoparticles of pullulan acetate/oligo-sulfonamide conjugate.

pH-sensitive hydrogel nanoparticles that respond to the local acidic pH found in various diseased states such as tumors, ischemia and inflammation were prepared from pullulan acetate/oligo-sulfadimethoxine (PA/OSDM) conjugates. PA/OSDM nanoparticles prepared by dialysis at pH 9.5 had a spherical shape with a size range of 50-140 nm and low critical aggregation concentration (CAC) (<12 x 10(-3) mg/ml), dependent on the degree of substitution of OSDM (DS). With a decrease in dialysis pH (pHdia), the CAC gradually decreased due to the increase in the hydrophobic nature of OSDM. The nanoparticles prepared at pHdia 8.0 from the polymer with DS 1.0 aggregated in a pH range of 6.6-7.2 while the aggregation of nanoparticles prepared below pHdia 7.4 occurred in a broader pH range with a downshifted transition pH. These results indicate that the CAC and sharpness of the pH sensitivity of self-assembled hydrogel nanoparticles can be controlled by the pH of the dialysis buffer. In addition, the photophysical and photochemical characteristics of the nanoparticles were examined by a fluorescence probe technique. The micropolarity was monitored by pyrene and the microviscosity was measured by 1,6-diphenyl-1,3,5,-hexatriene (DPH) in the core of nanoparticles. Both properties dramatically changed as the pH decreased from 7.2 to 6.8, indicating that the interior restructuring of the hydrogel nanoparticles changed rapidly in this pH range. This is probably due to recruitment of hydrophobic group of deionized OSDM into the core. The pH sensitivity of the nanoparticles affected their drug release behavior. Doxorubicin (DOX) release from the PA/OSDM nanoparticles showed pH-dependent profiles around physiological pH and was significantly promoted at pH<6.8.

Acetates↗

Preparation of nanoparticles composed of poly(gamma-glutamic acid)-poly(lactide) block copolymers and evaluation of their uptake by HepG2 cells.

In the study, poly(gamma-glutamic acid) (gamma-PGA) and poly(lactide) (PLA) were used to synthesize block copolymers via a simple coupling reaction between gamma-PGA and PLA to prepare self-assembled nanoparticles. For the potential of targeting liver cancer cells, galactosamine was further conjugated on the prepared nanoparticles as a targeting moiety. gamma-PGA, a water-soluble, biodegradable, and non-toxic compound, was produced by microbial fermentation (Bacillus licheniformis, ATCC 9945a) and then was hydrolyzed. The hydrolyzed gamma-PGA with a molecular weight of 4 kDa and a polydispersity of 1.3 was used, together with PLA (10 kDa, polydispersity 1.1), to synthesize block copolymers. The prepared nanoparticles had a mean particle size of about 140 nm with a zeta potential of about -20 mV. The results obtained by the TEM and AFM examinations showed that the morphology of the prepared nanoparticles was spherical in shape with a smooth surface. In the stability study, no aggregation or precipitation of nanoparticles was observed during storage for up to 1 month, as a result of the electrostatic repulsion between the negatively charged nanoparticles. With increasing the galactosamine content conjugated on the rhodamine-123-containing nanoparticles, the intensity of fluorescence observed in HepG2 cells increased significantly. Additionally, the intensity of fluorescence observed in HepG2 cells incubated with the nanoparticles with or without galactosamine conjugated increased approximately linearly with increasing the duration of incubation. In contrast, there was no fluorescence observed in Hs68 cells (without ASGP receptors) incubated with the nanoparticles with galactosamine conjugated. The aforementioned results indicated that the galactosylated nanoparticles prepared in the study had a specific interaction with HepG2 cells via ligand-receptor recognition.

Cell Line, Tumor↗

Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system.

In this study, the potential of N-trimethyl chitosan (TMC) nanoparticles as a carrier system for the nasal delivery of proteins was investigated. TMC nanoparticles were prepared by ionic crosslinking of TMC solution (with or without ovalbumin) with tripolyphosphate, at ambient temperature while stirring. The size, zeta-potential and morphology of the nanoparticles were investigated as a function of the preparation conditions. Protein loading, protein integrity and protein release were studied. The toxicity of the TMC nanoparticles was tested by ciliary beat frequency measurements of chicken embryo trachea and in vitro cytotoxicity assays. The in vivo uptake of FITC-albumin-loaded TMC nanoparticles by nasal epithelia tissue in rats was studied by confocal laser scanning microscopy. The nanoparticles had an average size of about 350 nm and a positive zeta-potential. They showed a loading efficiency up to 95% and a loading capacity up to 50% (w/w). The integrity of the entrapped ovalbumin was preserved. Release studies showed that more than 70% of the protein remained associated with the TMC nanoparticles for at least 3 h on incubation in PBS (pH 7.4) at 37 degrees C. Cytotoxicity tests with Calu-3 cells showed no toxic effects of the nanoparticles, whereas a partially reversible cilio-inhibiting effect on the ciliary beat frequency of chicken trachea was observed. In vivo uptake studies indicated the transport of FITC-albumin-associated TMC nanoparticles across the nasal mucosa. In conclusion, TMC nanoparticles are a potential new delivery system for transport of proteins through the nasal mucosa.

Animals↗

A study on the sizes and concentrations of gold nanoparticles by spectra of absorption, resonance Rayleigh scattering and resonance non-linear scattering.

Liquid phase gold nanoparticles with different diameters and colors can be prepared using sodium citrate reduction method by controlling the amounts of sodium citrate. The mean diameters of gold nanoparticles are measured by transmission electron microscope (TEM). Gold nanoparticles with different sizes have specific absorption spectra. When the diameters of nanoparticles is between 12 and 41 nm, the maximum absorption peaks locate at 520-530 nm and there are red shifts gradually with the increase of diameters of gold nanoparticles. And when the size of gold nanoparticle is constant, the absorbance is proportional to the concentration of gold. Obvious resonance Rayleigh scattering (RRS) and the resonance non-linear scattering such as second-order scattering (SOS) and frequency-doubling scattering (FDS) appear at the same time as well, and the maximum scattering peaks are located at 286 nm (RRS), 480 nm (SOS) and 310 nm (FDS), respectively. When the concentration of gold is constant, absorbance and the intensities of RRS, SOS and FDS (I(RRS), I(SOS) and I(FDS)) have linear relationships with the diameters of gold nanoparticles. When the diameter of gold nanoparticle is constant, the absorbance and I(RRS), I(SOS), I(FDS) are directly proportional to the concentrations of gold nanoparticles. Therefore, it is very useful for studying the liquid phase gold nanoparticles by investigating the absorption, RRS, SOS and FDS spectra.

Color↗

Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems.

Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

Administration, Intranasal↗

Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake.

Superparamagnetic magnetite nanoparticles were surface-modified with poly (ethylene glycol) (PEG) and folic acid, respectively, to improve their intracellular uptake and ability to target specific cells. PEG and folic acid were successfully immobilized on the surfaces of magnetite nanoparticles and characterized using fourier transform infrared spectra. The nanoparticle internalization into mouse macrophage (RAW 264.7) and human breast cancer (BT20) cells was visualized using both fluorescence and confocal microscopy, and quantified by inductively coupled plasma emission spectroscopy (ICP). After the cells were cultured for 48 h in the medium containing the nanoparticles modified with PEG or folic acid, the results of fluorescence and confocal microscopy showed that the nanoparticles were internalized into the cells. The ICP measurements indicated that the uptake amount of PEG-modified nanoparticles into macrophage cells was much lower than that of unmodified nanoparticles. while folic acid modification did not change the amount of the uptake. However, for breast cancer cells, both PEG and folic acid modification facilitated the nanoparticle internalization into the cells. Therefore, PEG and folic acid modification of magnetite nanoparticles could be used to resist the protein adsorption and thus avoid the particle recognition by macrophage cells, and to facilitate the nanoparticle uptake to specific cancer cells for cancer therapy and diagnosis.

Animals↗