Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

Transdermal drug delivery(TDD) can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow–green fluorescent nanoparticles and high molecular weight hyaluronic acid(HA) in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that,with the application of ultrasound exposures, the permeability of the skin to these markers(e.g., their penetration depth and concentration) could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents(UCAs). When the ultrasound was applied without UCAs,low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 μm. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 μm, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4–5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications(e.g., nanoparticle drug carriers, transdermal patches and cosmetics), protocols and methods presented in this paper are potentially useful.     

Magnetic lipid nanoparticles loading doxorubicin for intracellular delivery: Preparation and characteristics

Tumor intracellular delivery is an effective route for targeting chemotherapy to enhance the curative effect and minimize the side effect of a drug. In this study, the magnetic lipid nanoparticles with an uptake ability by tumor cells were prepared dispersing ferroso-ferric oxide nanoparticles in aqueous phase using oleic acid (OA) as a dispersant, and following the solvent dispersion of lipid organic solution. The obtained nanoparticles with 200 nm volume average diameter and −30 mV surface zeta potential could be completely removed by external magnetic field from aqueous solution. Using doxorubicin (DOX) as a model drug, the drug-loaded magnetic lipid nanoparticles were investigated in detail, such as the effects of OA, drug and lipid content on volume average diameter, zeta potential, drug encapsulation efficiency, drug loading, and in vitro drug release. The drug loading capacity and encapsulation efficiency were enhanced with increasing drug or lipid content, reduced with increasing OA content. The in vitro drug release could be controlled by changing drug or lipid content. Cellular uptake by MCF-7 cells experiment presented the excellent internalization ability of the prepared magnetic lipid nanoparticles. These results evidenced that the present magnetic lipid nanoparticles have potential for targeting therapy of antitumor drugs.     

Magnetic nanoparticles for local drug delivery using magnetic implants

Magnetic nanoparticles are good candidates used for the targeted delivery of anti-tumor agents. They can be concentrated on a desired region, reducing collateral effects and improving the efficiency of the chemotherapy. We propose a method in which permanent magnets are implanted by laparoscopic technique directly in the affected organ. This method proposes the use of Fe@C nanoparticles, which are loaded with doxorubicin and injected intravenously. The particles, once attracted to the magnet, release the drug at the tumor region. This method seems to be more promising and effective than that based on the application of external magnetic fields.     

Functionalized magnetic nanoparticles for drug delivery in tumor therapy

The side effects of chemotherapy are mainly the poor control of drug release. Magnetic nanoparticles(MNPs) have super-paramagnetic behaviors which are preferred for biomedical applications such as in targeted drug delivery, besides, in magnetic recording, catalysis, and others. MNPs, due to high magnetization response, can be manipulated by the external magnetic fields to penetrate directly into the tumor, thus they can act as ideal drug carriers. MNPs also play a crucial role in drug delivery system because of their high surface-to-volume ratio and porosity. The drug delivery in tumor therapy is related to the sizes, shapes, and surface coatings of MNPs as carriers. Therefore, in this review, we first summarize the effects of the sizes, shapes, and surface coatings of MNPs on drug delivery, then discuss three types of drug release systems, i.e., p H-controlled, temperature-controlled, and magnetic-controlled drug release systems, and finally compare the principle of passive drug release with that of active drug release in tumor therapy.     

Polyarginine nanocapsules: a new platform for intracellular drug delivery

This report describes the development of a new nanocarrier, named as polyarginine (PArg) nanocapsules, specifically designed for overcoming cellular barriers. These nanocapsules are composed of an oily core and a PArg corona. The attachment of the PArg corona was mediated by its interaction with the oily core, which was conveniently stabilized with phosphatidylcholine. Hybrid PArg/PEG nanocapsules could also be obtained by introducing PEG-stearate in the nanocapsules formation process. The nanocapsules had an average size in the range of 120–160 nm, and a positive surface charge, which varied between +56 and +28 mV for PArg and PArg/PEG nanocapsules, respectively. They could accommodate significant amounts of lipophilic drugs, i.e., docetaxel, in their core, and also polar negatively charged molecules, i.e., plasmid DNA, on their coating. As a preliminary proof-of-principle, we explored the ability of these nanocarriers to enter cancer cells and to inhibit proliferation in the non-small cell lung cancer NCI-H460 cell line, using flow cytometry and confocal microscopy analysis. The results indicated that PArg nanocapsules are rapidly and massively accumulated into the NCI-H460 cells and that the PArg shell plays a critical role in the internalization process. Moreover, the incubation with docetaxel-loaded nanocapsules with NCI-H460 cells led to an enhanced inhibition of their proliferation, as compared to the free drug. Overall, this is the first report of the potential of PArg nanocapsules as intracellular drug delivery vehicles.

     

Dual pH-responsive and CD44 receptor targeted multifunctional nanoparticles for anticancer intracellular delivery

Journal of Nanoparticle Research - Photochemical synthesis of selected multicomponent compounds, namely cadmium or magnesium zinc oxides doped with Ga3+ ions—Zn1?x Cd x (Mg x...     

Facile method for CLSM imaging unfunctionalized Au nanoparticles through fluorescent channels

The microscopic visualization of metal nanoparticles has become a useful tool for the investigation of their applications in cell labeling and the study of their bio-effects. In the current study, we have developed a facile method with confocal laser scanning microscope (CLSM) to observe unfunctionalized Au nanoparticles through fluorescent channels. The sharp reflected signal and photostable property of the metal nanoparticles makes the present method very ideal for fluorescent co-localization, real-time imaging, and further quantitative analysis. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Lan Yuan and Wei Wei contributed equally to this study.     

Nonlinear optical microscopy for drug delivery monitoring and cancer tissue imaging

A multimodal nonlinear optical microscope that combines coherent anti‐Stokes Raman scattering (CARS), two‐photon excitation fluorescence (TPEF), second‐harmonic generation (SHG) and sum‐frequency generation (SFG) was developed and applied to image breast cancer tissue and MCF‐7 cells as well as monitoring anticancer drug delivery in live cells. TPEF imaging showed that drugs are preferentially localized in the cytoplasm and the nuclear envelope in resistant cells. Moreover, the extracellular matrix was observed by TPEF signals arising from elastin's autofluorescence and SHG signals from collagen fibrils in breast tissue sections. Additionally, CARS signals arising from proteins and (PO₂)⁻ allowed identification of tumors. Label‐free imaging with chemical contrast of significant components of cancer cells and tissue suggests the potential of multimodal nonlinear optical microscopy for early detection and diagnosis of cancer. Copyright © 2010 John Wiley & Sons, Ltd.     

Photo-synthesis of protein-based nanoparticles and the application in drug delivery

Recently, protein-based nanoparticles as drug delivery systems have attracted great interests due to the excellent behavior of high biocompatibility and biodegradability, and low toxicity. However, the synthesis techniques are generally costly, chemical reagents introduced, and especially present difficulties in producing homogeneous monodispersed nanoparticles. Here, we introduce a novel physical method to synthesize protein nanoparticles which can be accomplished under physiological condition only through ultraviolet (UV) illumination. By accurately adjusting the intensity and illumination time of UV light, disulfide bonds in proteins can be selectively reduced and the subsequent self-assembly process can be well controlled. Importantly, the co-assembly can also be dominated when the proteins mixed with either anti-cancer drugs, siRNA, or active targeting molecules. Both in vitro and in vivo experiments indicate that our synthesized protein–drug nanoparticles (drug-loading content and encapsulation efficiency being ca. 8.2% and 70%, respectively) not only possess the capability of traditional drug delivery systems (DDS), but also have a greater drug delivery efficiency to the tumor sites and a better inhibition of tumor growth (only 35% of volume comparing to the natural growing state), indicating it being a novel drug delivery system in tumor therapy.     

Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery into cancer cells

A certified reference material, ERM-FD100, for quality assurance and validation of various nanoparticle sizing methods, was developed by the Institute for Reference Materials and Measurements. The material was prepared from an industrially sourced colloidal silica containing nanoparticles with a nominal equivalent spherical diameter of 20?nm. The homogeneity and stability of the candidate reference material was assessed by means of dynamic light scattering and centrifugal liquid sedimentation. Certification of the candidate reference material was based on a global interlaboratory comparison in which 34 laboratories participated with various analytical methods (DLS, CLS, EM, SAXS, ELS). After scrutinising the interlaboratory comparison data, 4 different certified particle size values, specific for the corresponding analytical method, could be assigned. The good comparability of results allowed the certification of the colloidal silica material for nanoparticle size analysis.     

Lipid-based nanoparticles as drug delivery system for paclitaxel in breast cancer treatment

Paclitaxel (PTX) is a well-known antitumor drug, widely utilized in the treatment of breast, ovarian, head, and neck tumors, among others. The low aqueous solubility (< 1.0 μg/mL; log P = 3.96) limits its use by intravenous route, and alternatives found for the marketed products are associated with high toxicity. Incorporation of PTX into lipid nanocarriers has been considered an interesting nontoxic alternative for this route, but drug loading is usually low. This study aimed to analyze the influence of the lipid composition and three different lipid nanosystems—solid lipid nanoparticles, nanostructured lipid carriers (NLCs), and nanoemulsion—in PTX encapsulation and its biological response. The three proposed systems were prepared by hot melt homogenization followed by ultrasonication. Among the blank formulations first prepared, NLC had the smallest size (74 ± 1 nm), with negative zeta potential (? 11.4 ± 0.1 mV). The incorporation of 0.10 mg/mL PTX into this NLC formulation yielded high and stable encapsulation (0.089 ± 0.003 mg/mL), also supported by polarized light microscopy and differential scanning calorimetry curves. NLC-PTX was very effective against MCF-7 (IC50 25.33 ± 3.17 nM) and MDA-MB-231 breast cancer cell lines (IC50 2.13 ± 0.21 nM), compared to free PTX (IC50 > 500 nM). In addition, no significant cytotoxicity was found against fibroblast cells. Taken together, these results demonstrated that PTX was successfully incorporated into NLC with appropriate physicochemical characteristics for intravenous administration, suggesting that the use of NLC as vehicle to incorporate PTX may be a promising strategy in the treatment of breast cancer.     

Polymeric nanoparticles assembled with microfluidics for drug delivery across the blood-brain barrier

The blood-brain barrier (BBB) is a challenge in the treatment of some diseases, since it prevents many drugs from reaching therapeutic concentrations in the brain. In this context, there is a growing interest in nanoparticles for drug delivery, since they are able to cross this barrier and target the brain. The use of polymeric materials in the development of these nanoparticles has been extensively studied. It has already been demonstrated that these nanosystems have the ability to cross the BBB, which allows effective drug release into the brain. Biodegradable polymers provide a great advantage in the development of nanosystems, but modifications of the nanoparticles’ surface is essential. The traditional batch methods lack precise control over the processes of nucleation and growth, resulting in poor control over final properties of the nanoparticles. Therefore, microfluidics could be used to achieve a better production environment for the fabrication of nano- structured drug delivery systems. This study provides a brief review of: the BBB, the polymeric nanoparticles with the ability to overcome the barrier, the properties of the most used polymeric matrices, and the nanostructured drug delivery systems assembled with microfluidics.     

超声联合微泡增强细胞内药物递送的研究进展

超声联合微泡介导的细胞内药物递送是通过微泡的声空化与细胞的相互作用而实现的.作为一种非侵入式的、非病毒的、具有靶向性的、可在成像技术引导下的药物递送技术,超声联合微泡在临床应用上具有独特的优势.该文围绕超声联合微泡实现药物递送的发生机理,从微泡的声学动态响应、细胞响应、细胞外物质进入细胞的动态过程及临床试验进展4方面对...     

Effects of surfactants on properties of polymer-coated magnetic nanoparticles for drug delivery application

The objective of this research was to compare the effects of two different surfactants on the physicochemical properties of thermo-responsive poly(N-isopropylacrylamide-acrylamide-allylamine) (PNIPAAm-AAm-AH)-coated magnetic nanoparticles (MNPs). Sodium dodecyl sulfate (SDS) as a commonly used surfactant in nanoparticle formulation process and Pluronic F127 as an FDA approved material were used as surfactants to synthesize PNIPAAm-AAm-AH-coated MNPs (PMNPs). The properties of PMNPs synthesized using SDS (PMNPs-SDS) and PF127 (PMNPs-PF127) were compared in terms of size, polydispersity, surface charge, drug loading efficiency, drug release profile, biocompatibility, cellular uptake, and ligand conjugation efficiency. These nanoparticles had a stable core–shell structure with about a 100-nm diameter and were superparamagnetic in behavior with no difference in the magnetic properties in both types of nanoparticles. In vitro cell studies showed that PMNPs-PF127 were more cytocompatible and taken up more by prostate cancer cells than that of PMNPs-SDS. Cells internalized with these nanoparticles generated a dark negative contrast in agarose phantoms for magnetic resonance imaging. Furthermore, a higher doxorubicin release at 40 °C was observed from PMNPs-PF127, and the released drugs were pharmacologically active in killing cancer cells. Finally, surfactant type did not affect the conjugation efficiency to the nanoparticles when folic acid was used as a targeting ligand model. These results indicate that PF127 might be a better surfactant to form polymer-coated magnetic nanoparticles for targeted and controlled drug delivery.     

Biodegradable thermoresponsive polymeric magnetic nanoparticles: a new drug delivery platform for doxorubicin

The use of nanoparticles as drug delivery systems for anticancer therapeutics has great potential to revolutionize the future of cancer therapy. The aim of this study is to construct a novel drug delivery platform comprising a magnetic core and biodegradable thermoresponsive shell of tri-block-copolymer. Oleic acid-coated Fe₃O₄ nanoparticles and hydrophilic anticancer drug “doxorubicin” are encapsulated with PEO–PLGA–PEO (polyethylene oxide–poly d, l lactide-co-glycolide–polyethylene oxide) tri-block-copolymer. Structural, magnetic, and physical properties of Fe₃O₄ core are determined by X-ray diffraction, vibrating sample magnetometer, and transmission electron microscopy techniques, respectively. The hydrodynamic size of composite nanoparticles is determined by dynamic light scattering and is found to be ~36.4 nm at 25 °C. The functionalization of magnetic core with various polymeric chain molecules and their weight proportions are determined by Fourier transform infrared spectroscopy and thermogravimetric analysis, respectively. Encapsulation of doxorubicin into the polymeric magnetic nanoparticles, its loading efficiency, and kinetics of drug release are investigated by UV–vis spectroscopy. The loading efficiency of drug is 89% with a rapid release for the initial 7 h followed by the sustained release over a period of 36 h. The release of drug is envisaged to occur in response to the physiological temperature by deswelling of thermoresponsive PEO–PLGA–PEO block-copolymer. This study demonstrates that temperature can be exploited successfully as an external parameter to control the release of drug.     

Ratiometric fluorescent nanoparticles for sensing temperature

A ratiometric type of fluorescent nanoparticle was prepared via an encapsulation–reprecipitation method. By introducing an alkoxysilanized dye as a reference, the nanoparticles (NPs) give both a green and a red fluorescence under one single-wavelength excitation. The resulted ratiometric fluorescence is found to be highly temperature-dependent in the physiological range (25–45 °C), with an intensity temperature sensitivity of ?4.0%/°C. Given the small size (20–30 nm in diameter) and biocompatible nature (silica out layer), such kind of NPs were very promising as temperature nanosensors for cellular sensing and imaging.     

Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system

Nanoparticles can be used in biomedical applications, where they facilitate laboratory diagnostics, or in medical drug targeting. They are used for in vivo applications such as contrast agent for magnetic resonance imaging (MRI), for tumor therapy or cardiovascular disease. Very promising nanoparticles for these applications are superparamagnetic nanoparticles based on a core consisting of iron oxides (SPION) that can be targeted through external magnets. SPION are coated with biocompatible materials and can be functionalized with drugs, proteins or plasmids. In this review, the characteristics and applications of SPION in the biomedical sector are introduced and discussed.     

Leucine-coated cobalt ferrite nanoparticles: Synthesis,characterization and potential biomedical applications for drug delivery

This work was primarily focused on the synthesis, characterization and biomedical applications of cobalt ferrite (CoFe₂O₄) nanoparticles, which were synthesized by a facile solvothermal method using an amino acid of Leucine (Leu) as the surface coating agents. The morphology, structure and properties of the as-synthesized uncoated and Leu-coated CoFe₂O₄ nanoparticles were characterized in detail by means of XRD, SEM, TEM, DLS, FTIR, XPS, TGA and SQUID. More importantly, it was found that the Leu-coated CoFe₂O₄ nanoparticles can be used as the efficient drug delivery with a drug loading capacity of 0.32 mg/mg for doxorubicin hydrochloride (DOX), and the loaded DOX demonstrated a sustained and progressive release manner. The in vitro cytotoxicity studies towards the HeLa cells were carried out, and the results indicated that the Leu-coated CoFe₂O₄ nanoparticles exhibited a relatively high cell viability compared with that of bare CoFe₂O₄ nanoparticles and the DOX loaded Leu-coated CoFe₂O₄ nanoparticles presented an obvious cytotoxic effect on HeLa cells.