Nanomedicine: Nanotechnology, Biology and Medicine

Novel sorbents for removal of gadolinium-based contrast agents in sorbent dialysis and hemoperfusion: preventive approaches to nephrogenic systemic fibrosis

2009-05-18

Abstract: Many forms of organocomplexed gadolinium (Gd) contrast agents have recently been linked to a debilitating and a potentially fatal skin disease called nephrogenic systemic fibrosis (NSF) in patients with renal failure. Free Gd released from these complexes via transmetallation is believed to be the most important trigger for NSF. In this work, nanostructure silica materials that have been functionalized with 1-hydroxy-2-pyridinone (1,2-HOPO-SAMMS) have been evaluated for selective and effective removal of both free and chelated Gd (gadopentetate dimeglumine and gadodiamide) from dialysate and blood. 1,2-HOPO SAMMS has high affinity, rapid removal rate, and large sorption capacity for both free and chelated Gd, properties that are far superior to those of activated carbon and zirconium phosphate currently used in the state-of-the-art sorbent dialysis and hemoperfusion systems. The SAMMS-based sorbent dialysis and hemoperfusion will potentially provide an effective and predicable strategy for removing the Gd from patients with impaired renal function after Gd exposure, thus allowing for the continued use of Gd-based contrast magnetic resonance imaging while removing the risk of NSF.From the Clinical Editor: Chelated gadolinium (Gd) contrast agents have been linked to a debilitating disease called nephrogenic systemic fibrosis (NSF) in patients with renal failure. Free Gd+3 released from the contrast agents is believed to be the trigger for NSF. In this work, functionalized nanostructured silica materials were evaluated for removal of both free and chelated gadolinium both from dialysate and blood. The new method demonstrated a rapid removal rate and large sorption capacity, and overall was far superior to currently used state-of-the-art sorbent dialysis and hemoperfusion systems.

Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery

B. Mishra, Bhavesh B. Patel, Sanjay Tiwari — 2009-05-18

Abstract: Colloidal nanocarriers, in their various forms, have the possibility of providing endless opportunities in the area of drug delivery. The current communication embodies an in-depth discussion of colloidal nanocarriers with respect to formulation aspects, types, and site-specific drug targeting using various forms of colloidal nanocarriers with special insights to the field of oncology. Specialized nanotechnological approaches like quantum dots, dendrimers, integrins, monoclonal antibodies, and so forth, which have been extensively researched for targeted delivery of therapeutic and diagnostic agents, are also discussed. Nanotechnological patents, issued by the U.S. Patent and Trademark Office in the area of drug delivery, are also included in this review to emphasize the importance of nanotechnology in the current research scenario.From the Clinical Editor: Colloidal nanocarriers provide almost endless opportunities in the area of drug delivery. While the review mainly addresses potential oncological applications, similar approaches may be applicable in other conditions with a requirement for targeted drug delivery. Technologies including quantum dots, dendrimers, integrins, monoclonal antibodies are discussed, along with US-based patents related to these methods.

Dendrimer nanocarriers as versatile vectors in gene delivery

Tathagata Dutta, Narendra K. Jain, Nigel A.J. McMillan, Harendra S. Parekh — 2009-05-18

Abstract: The successful delivery of nucleic acids to particular target sites is the challenge that is being addressed using a variety of viral and nonviral delivery systems, both of which have distinct advantages and disadvantages. Nonviral vectors offer the advantage of safety and flexibility over viral vectors, although they lack efficiency. Dendrimers are novel, three-dimensional polymers that have the ability to interact with various forms of nucleic acids such as plasmid DNA, antisense oligonucleotides, and RNA to form complexes that protect the nucleic acid from degradation. The interaction between the dendrimers and the nucleic acids is purely electrostatic where the cationic dendrimer condenses the anionic nucleic acids. Because cell membranes are negatively charged, the net positive charge of the dendrimer nucleic acid complex determines the transfection efficiency, although highly cationic systems are also cytotoxic. The nature of the dendrimer nucleic acid complex depends on various factors like stoichiometry, concentration of dendrimer-amines and nucleic acid-phosphates, as well as bulk solvent properties like pH, salt concentration, buffer strength, and dynamics of mixing. This article aims to review the role of dendrimers as novel gene delivery vectors both in vitro and in vivo. Dendrimer-based transfection reagents have become routine tools for in vitro transfection, but in vivo delivery of therapeutic nucleic acids remains a challenge.From the Clinical Editor: This review discusses the role of dendrimers as novel gene delivery vectors both in vitro and in vivo. Dendrimer based transfection reagents have become routine tools for in vitro transfection but in vivo delivery of therapeutic nucleic acids remains a challenge.

Osteoblasts response to microstructured and nanostructured polyimide film, processed by the use of silica bead microlenses

Muriel Voisin, Michael Ball, Claire O'Connell, Richard Sherlock — 2009-06-05

Abstract: The surface of polyimide ﬁlms was modiﬁed by the use of silica microspheres as microlenses to focus radiation emitted by an excimer laser. The resultant surface had both microstructures and nanostructures. Physical and chemical characterization was performed by atomic force and Fourier transform–infrared microscopy. Laser processing resulted in surfaces that had similar roughness but different component frequencies. Chemical changes were not observed with the techniques used. The response of osteoblasts to the surface was assayed by measuring their metabolic activity and the enzyme alkaline phosphatase activity, after 24 hours of growth. Cytoskeleton and expression were both investigated. Metabolic activity was similar on treated and untreated samples. Total cell number and size were increased on microstructured polymer, where speciﬁc structures were observed (protrusions). Adhesion was noted, and the actin cytoskeleton showed normal morphology. Cells on nanostructured samples had a diffuse actin network and less mature adhesions as compared with the control.From the Clinical Editor: Polyimide films with microstructure and nanostructure surface elements were studied from the standpoint of osteoblast response. Total cell number and size were increased on microstructured polymer and protrusions were also observed. Adhesion was noted and the actin cytoskeleton exhibited normal morphology. Cells on nanostructured samples had a diffuse actin network and less mature adhesions.

The role of surface energy of technical polymers in serum protein adsorption and MG-63 cells adhesion

Jordi Comelles, Maruxa Estévez, Elena Martínez, Josep Samitier — 2009-06-05

Abstract: Polymeric materials are widely used as supports for cell culturing in medical implants and as scaffolds for tissue regeneration. However, novel applications in the biosensor field require materials to be compatible with cell growth and at the same time be suitable for technological processing. Technological polymers are key materials in the fabrication of disposable parts and other sensing elements. As such, it is essential to characterize the surface properties of technological polymers, especially after processing and sterilization. It is also important to understand how technological polymers affect cell behavior when in contact with polymer materials. Therefore, the aim of this research was to study how surface energy and surface roughness affect the biocompatibility of three polymeric materials widely used in research and industry: poly(methyl methacrylate), polystyrene, and poly(dimethylsiloxane). Glass was used as the control material.From the Clinical Editor: Polymeric materials are widely used as supports for cell culturing in medical implants and as scaffolds for tissue regeneration. The aim of this research is to study how surface energy and surface roughness affect the biocompatibility of three polymeric materials widely used in research and industry: poly(methylmethacrylate) (PMMA), polystyrene (PS), and poly(dimethylsiloxane) (PDMS).

Simultaneous detection of dopamine, ascorbic acid, and uric acid at electrochemically pretreated carbon nanotube biosensors

Subbiah Alwarappan, Guodong Liu, Chen-Zhong Li — 2009-07-21

Abstract: In this work we have evaluated the performance of electrochemically pretreated single-walled carbon nanotubes (SWCNTs) toward the electrochemical detection of dopamine in the presence of ascorbic acid and uric acid at physiological pH. Results indicated that the electrochemically pretreated SWCNTs showed a selective and enhanced electroanalytical response with minimal electrode fouling toward the detection of dopamine than their untreated counterparts. The observed behavior is attributed to the negatively charged layer present on the SWCNTs originating from the rupture of the basal plane present on the end caps following electrochemical pretreatment. The rupture of basal plane is evident from surface Raman measurements. The negatively charged surface selectively allows the cationic dopamine toward the electrode and repels the anionic ascorbate and uric acid when they coexist in the same solution under physiological pH. A limit of detection of about 15 nM is obtained with these electrodes for the detection of dopamine in the presence of ascorbic acid and uric acid.From the Clinical Editor: The performance of electrochemically pretreated single-walled carbon nanotubes (SWCNTs) was studied toward the electrochemical detection of dopamine. These SWCNTs showed a selective and enhanced response toward the detection of dopamine. A limit of detection of about 15 nM is obtained with these electrodes for the detection of dopamine in the presence of ascorbic acid and uric acid.

Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method

2009-05-18

Abstract: In the past decade, many strategies have been developed to enhance oral protein delivery. The aim of the current work was to develop a nanoparticulate system based on ionic gelation between chitosan and Arabic gum for loading of insulin. Various formulations were prepared using 23 factorial designs. The optimum association efficiency was obtained for formulations F2, F5, and F8. The release profile of insulin in phosphate buffer solutions (pH 6.5 and pH 7.2) is completely different than that in acidic medium (pH 1.2). Increased solubility of chitosan in acidic medium and better swelling of Arabic gum chains at pH >6.5 resulted in lower insulin release of nanoparticles at pH 6.5 in comparison with that of the other pH mediums. The values of the exponent n were 0.49 and 0.82 for formulations F8 and F5, respectively, indicating a non-Fickian transport. This suggests that release is possibly controlled by diffusion or relaxation of the polymer chains.From the Clinical Editor: This paper summarizes the development of a nanoparticulate system based on ionic gelation between chitosan and gum Arabic for oral delivery of insulin. If preclinical studies in animal models will indicate reliable and quantifiable delivery of insulin, this method may pave the way to a novel and less invasive way of administering insulin to diabetes patients.

Multifunctional magnetic nanoparticles for targeted delivery

2009-05-18

Abstract: A major problem associated with drug therapy is the inability to deliver pharmaceuticals to a specific site of the body without causing nonspecific toxicity. Development of magnetic nanoparticles and techniques for their safe transport and concentration in specific sites in the body would constitute a powerful tool for gene/drug therapy in vivo. Furthermore, drug delivery in vitro could improve further if the drugs were modified with antibodies, proteins, or ligands. For in vivo experiments, magnetic nanoparticles were conjugated with plasmid DNA expressing enhanced green fluorescent protein (EGFP) and then coated with chitosan. These particles were injected into mice through the tail vein and directed to the heart and kidneys by means of external magnets of 25 gauss or 2kA–kA/m. These particles were concentrated in the lungs, heart, and kidneys of mice, and the expression of EGFP in these sites were monitored. The expression of EGFP in specific locations was visualized by whole-body fluorescent imaging, and the concentration of these particles in the designated body locations was confirmed by transmission electron microscopy. In another model system, we used atrial natriuretic peptide and carcinoembryonic antigen antibodies coupled to the chitosan-coated magnetic nanoparticles to target cells in vitro. The present work demonstrates that a simple external magnetic field is all that is necessary to target a drug to a specific site inside the body without the need to functionalize the nanoparticles. However, the option to use magnetic targeting with external magnets on functionalized nanoparticles could prove as a more efficient means of drug delivery.From the Clinical Editor: This paper addresses targeted drug delivery with magnetic nanoparticles. The authors demonstrate that a simple external magnetic field is sufficient to target a drug to specific sites in the body without the need for functionalized nanoparticles, at least in selected organs and diseases.

Evaluation of cationic liposomes composed of an amino acid–based lipid for neuronal transfection

2009-05-18

Abstract: We investigated the ability of cationic liposomes composed of 1,5-dihexadecyl N-arginyl-L-glutamate (Arg-Glu2C16) to carry nucleic acids into neuronal cells. Such liposomes have been shown to have a remarkable capacity for transfecting immortalized cell lines. Lipoplexes between the Arg-Glu2C16 liposomes and plasmid DNA encoding green fluorescent protein (GFP) were analyzed in terms of lipoplex formation, intracellular DNA trafficking, transfection efficiency, and cytotoxicity in neuronal SH-SY5Y cells. A maximum number of cells expressing GFP was obtained with lipoplexes at a lipid-to-DNA ratio of 15. With these lipoplexes, 16% of the cells were GFP-positive, which was approximately fourfold higher than the level obtained with a commercially available transfection reagent, Lipofectamine 2000. Furthermore, as a result of the low cytotoxicity of the Arg-Glu2C16 lipoplexes, the proportion of GFP-positive cells could be increased to 25% by increasing the concentration of lipoplexes that was applied to the cells. We have demonstrated that Arg-Glu2C16, as a model cationic amino acid–based lipid, has a high capability as a gene carrier, even for neuronal transfection.From the Clinical Editor: In this study, specific cationic liposomes were characterized as nucleic acid transfection agents for neuronal cells. A fourfold higher transfection rate with low cytotoxicity was reported compared to Lipofectamine 2000, a commercial reagent. The authors conclude that the studied cationic liposomes have a high capability as a gene carrier for neuronal transfection. This may become clinically significant in future gene therapy efforts of neuronal diseases.

Measurements of serum C-reactive protein levels in patients with gastric cancer and quantification using silicon nanowire arrays

2009-05-18

Abstract: We examined the levels of serum α-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen in 83 of 400 patients who had undergone surgery for gastric cancer and correlated these markers with stages of the disease. In addition, we measured C-reactive protein (CRP) concentrations in the sera of gastric cancer patients with silicon nanowire field-effect transistors (SiNW FETs) to determine whether SiNW FETs could be used to accurately sense CRP, a marker of inflammation and possible indicator of future progression of the cancer. We designed and fabricated SiNWs to be responsive to CRP. Of the 83 patients examined, six who showed marked elevation of CRP (>3 to 10 mg/dL, according to hospital laboratory measurements) were selected and subjected to measurement with the SiNW FETs. Our findings showed that SiNW-based sensors could be highly sensitive and specific in measuring CRP in the sera of postoperative patients and thus could represent a simple and quick method of prognostic evaluation in patients.From the Clinical Editor: In this study, silicon nanowire field effect transistors were fabricated to be responsive to C-reactive protein. The new technology resulted in highly sensitive and specific CRP sensors, which may greatly simplify this serum test for a variety of conditions where rapid, accurate and easily repeatable CRP measurements are needed.

In vitro proliferating cell models to study cytotoxicity of silica nanowires

2009-05-18

Abstract: Proliferating cells representing two disease models (HeLa and Panc 10.05 cells) and a more physiologically relevant cell model (3T3-L1 cells) were used to study the acute toxicologic effects of silica nanowires (NWs). Cellular responses to NW effects were determined over a 4- to 20-hour exposure time-course. Proliferation, viability, metabolic activity, and toxicologic mechanism (apoptosis vs. necrosis) data showed the following: 3 × 104 NWs per cell inhibited cell proliferation. The effect was rapid in HeLa cells, but 3T3-L1 and Panc 10.05 cells appeared to be more tolerant to NWs, effects being significant only after 20 or 16 hours, respectively. Cells of all three cell lines showed a significant reduction in cellular metabolic activity after 20 hours of treatment with NWs. Assay of NW-invoked mechanism of cell death (caspase 3/7 activity) indicated that apoptosis was minimally induced. Small but significant effects of NWs were detected in 3T3-L1 and HeLa cells after 20-hour treatment. No NW-induction of caspase 3/7 activity was detected for Panc 10.05 cells. Proliferating cells provide a sensitive model to study treatment with silica NWs. Silica NWs appeared to be well tolerated by these three cell lines at the doses tested. When effects were detected, cell necrosis and not apoptosis was the main mechanism of silica NW–induced cell death.From the Clinical Editor: In this study, three relevant cell culture models were used to study the acute toxicological effects of silica nanowires (NW). All cell lines cells showed a significant reduction in cellular metabolic activity after 20 h of treatment with NW. Overall, silica NW appeared to be well-tolerated by these cell lines at the tested doses. Cell necrosis as opposed to apoptosis was the main mechanism of silica NW-induced cell death.

Toxic and teratogenic silica nanowires in developing vertebrate embryos

2009-05-18

Abstract: Silica-based nanomaterials show promise for biomedical applications such as cell-selective drug delivery and bioimaging. They are easily functionalized, which allows for the conjugation or encapsulation of important biomolecules. Although recent in vitro studies suggested that silica-derived nanomaterials are nontoxic, in vivo studies of silica nanomaterial toxicity have not been performed. Using the embryonic zebrafish as a model system, we show that silica nanomaterials with aspect ratios greater than 1 are highly toxic (LD50 = 110 pg/g embryo) and cause embryo deformities, whereas silica nanomaterials with an aspect ratio of 1 are neither toxic nor teratogenic at the same concentrations. Silica nanowires also interfere with neurulation and disrupt expression of sonic hedgehog, which encodes a key midline signaling factor. Our results demonstrate the need for further testing of nanomaterials before they can be used as platforms for drug delivery.From the Clinical Editor: Silica-based nanomaterials show promise for biomedical applications such as cell-selective drug delivery and bioimaging. Using an embryonic zebrafish model system silica nanomaterials with aspect ratios greater than one were found to be highly toxic; whereas silica nanomaterials with an aspect ratio of one are neither toxic nor teratogenic. These results demonstrate the need for testing “nanomaterials" before they can be used as platforms for drug delivery.

Biogenic synthesis of silver nanoparticles and their synergistic effect with antibiotics: a study against gram-positive and gram-negative bacteria

2009-05-18

Abstract: The development of a reliable green chemistry process for the biogenic synthesis of nanomaterials is an important aspect of current nanotechnology research. Silver nanoparticles (AgNPs) have been known for their inhibitory and bactericidal effect. Resistance to antimicrobial agents by pathogenic bacteria has emerged in recent years and is a major challenge for the health care industry. In the present investigation the use of the fungus Trichoderma viride for the extracellular biosynthesis of AgNPs from silver nitrate solution is reported. It was observed that the aqueous silver (Ag+) ions, when exposed to a filtrate of T. viride, were reduced in solution, thereby leading to formation of extremely stable AgNPs. These AgNPs were characterized by means of several techniques. The nanoparticles show maximum absorbance at 420 nm on ultraviolet-visible spectra. The presence of proteins was identified by Fourier transform–infrared spectroscopy. The reduction of Ag+ ions to elemental silver was characterized by x-ray photoelectron spectrophotometry. Electrokinetic measurements (zeta potential) of AgNPs as a function of pH in 1 × 10−3 mol dm−3 aqueous solution were evaluated. The transmission electron micrograph revealed the formation of polydispersed nanoparticles of 5–40 nm, and the presence of elemental silver was confirmed by energy-dispersed spectroscopy analysis. The nanoparticles were also evaluated for their increased antimicrobial activities with various antibiotics against gram-positive and gram-negative bacteria. The antibacterial activities of ampicillin, kanamycin, erythromycin, and chloramphenicol were increased in the presence of AgNPs against test strains. The highest enhancing effect was observed for ampicillin against test strains. The result showed that the combination of antibiotics with AgNPs have better antimicrobial effects. A mechanism was also proposed to explain this phenomenon.From the Clinical Editor: Silver nanoparticles (Ag NP-s) represent an important nanomedicine-based advance in the fight against polyresistent bacteria. In this study, the fungus Trichoderma viride was utilized for extracellular biosynthesis of extremely stable Ag Nps. The antibacterial activities of kanamycin, erythromycin, chloramphenicol and especially of ampicillin were increased in the presence of Ag NPs against test strains.

Comparative evaluation of hepatitis B surface antigen–loaded elastic liposomes and ethosomes for human dendritic cell uptake and immune response

2009-05-18

Abstract: The aim of the present study was to evaluate two vesicular carrier systems, ethosomes and elastic liposomes loaded with hepatitis B surface antigen, for in vitro qualitative and quantitative uptake by human dendritic cells (DCs) and ability to stimulate T lymphocytes. Quantitative uptake of antigen-loaded carriers was documented by flow cytometry, and internalization of the systems by the DCs was studied using spectral bioimaging. Ability of antigen-pulsed DCs to stimulate autologous peripheral blood lymphocytes and levels of TH1/TH2 cytokines were also examined using flow cytometry. Both vesicular carrier systems as antigen delivery modules and DCs as antigen-presenting cells were able to generate a protective immune response. However, ethosomes were found to have higher internalizing ability and immunogenicity in comparison with elastic liposomes. These properties of ethosomes coupled with their skin-navigating potential, make it an attractive vehicle for development of a transcutaneous vaccine against hepatitis B in preference to elastic liposomes.From the Clinical Editor: Two carrier systems for more potent vaccine administration - ethosomes and elastic liposomes loaded with hepatitis B surface antigen – are compared. Ethosomes demonstrated higher internalizing ability and immunogenicity. Due to their known skin-navigating potential, ethosomes may represent an attractive vehicle for development of a transcutaneous vaccine against hepatitis B.

Beta-casein nanovehicles for oral delivery of chemotherapeutic drugs

Alina Shapira, Yehuda G. Assaraf, Yoav D. Livney — 2009-07-17

Abstract: Bovine β-casein (β-CN) is an abundant milk protein that is highly amphiphilic and self-assembles into stable micellar structures in aqueous solutions. Here we introduce a drug-delivery system comprising a model hydrophobic anticancer drug, mitoxantrone (MX), entrapped within β-CN–based nanoparticles. This novel drug-delivery system allows hydrophobic drugs to be thermodynamically stable in aqueous solutions for oral-delivery applications aimed at treatment of various disorders. The gastric digestibility of β-CN suggests possible targeting to stomach tumors. Dimethyl sulfoxide (DMSO)-dissolved MX was entrapped in β-CN nanoparticles by stirring this solution into phosphate-buffered β-CN solution. High-affinity MX–β-CN association was found (Ka = [2.15 ± 0.30] × 106 M-1). The optimal nanovehicle formation conditions were 1 mg/mL β-CN, ≤6% (vol/vol) DMSO in phosphate-buffer solution, 10 mM MX in DMSO, and a MX:β-CN molar-ratio of ∼4:1. Under these conditions, particles of 100 to 300-nm diameter were formed. β-CN nanoparticles may serve as effective oral-delivery nanovehicles for solubilization and stabilization of hydrophobic drugs.From the Clinical Editor: Bovine β-casein (β-CN) is an abundant milk-protein that is highly amphiphilic and self-assembles into stable micellar-structures in aqueous solutions. β-CN nanoparticles may serve as effective oral-delivery nanovehicles for solubilization and stabilization of hydrophobic drugs, as demonstrated in this study utilizing methotrexate.

Porous-wall hollow glass microspheres as novel potential nanocarriers for biomedical applications

2009-07-17

Abstract: Porous-wall hollow glass microspheres (PW-HGMs) are a novel form of glass material consisting of a 10- to 100-μm-diameter hollow central cavity surrounded by a 1-μm-thick silica shell. A tortuous network of nanometer-scale channels completely penetrates the shell. We show here that these channels promote size-dependent uptake and controlled release of biological molecules in the 3- to 8-nm range, including antibodies and a modified single-chain antibody variable fragment. In addition, a 6-nm (70-kDa) dextran can be used to gate the porous walls, facilitating controlled release of an internalized short interfering RNA. PW-HGMs remained in place after mouse intratumoral injection, suggesting a possible application for the delivery of anticancer drugs. The combination of a hollow central cavity that can carry soluble therapeutic agents with mesoporous walls for controlled release is a unique characteristic that distinguishes PW-HGMs from other glass materials for biomedical applications.From the Clinical Editor: Porous-wall hollow glass microspheres (PW-HGMs) are a novel form of glass microparticles with a tortuous network of nanometer-scale channels. These channels allow size-dependent uptake and controlled release of biological molecules including antibodies and single-chain antibody fragments. PW-HGMs remained in place after mouse intratumoral injection, suggesting a possible application for the delivery of anti-cancer drugs.

Preparation of chitosan nanoparticles containing Naja naja oxiana snake venom

2009-07-17

Abstract: Hydrophilic nanoparticles have received much attention for delivery of therapeutic peptides, proteins, and antigens. Chitosan (CS) is a biodegradable and nontoxic polysaccharide, as a carrier for drug delivery. The study purpose was to evaluate the influence of a number of factors on the encapsulation of Naja naja oxiana (Indian or speckled cobra) venom and loading capacity, as well as to investigate the physicochemical structure of nanoparticles. CS nanoparticles were produced based on the ionic gelation process of tripolyphosphate (TPP) and CS. All the preparations were estimated with diameter 120–150 nm and spherical shape using transmission electron microscopy. Fourier transform–infrared spectroscopy confirmed that tripolyphosphoric groups of TPP linked with ammonium groups of CS in the nanoparticles. Our results showed that CS can react with TPP to form stable cationic nanoparticles. Therefore, when chitosan concentration was increased to 1.5 mg/mL the aggregates with large diameter were formed. Optimum loading capacity and encapsulation efficiency of venom at a concentration of 500 μg/mL were achieved for low-molecular-weight (low-MW) CS at a concentration of 2 mg/mL and high-MW CS at a concentration of 3 mg/mL.From the Clinical Editor: In this study a hydrophilic nanoparticle chitosan was investigated as a protein delivery system, and optimum conditions were established for future use of this technology.

Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine

2009-05-18

Abstract: Tacrine-loaded chitosan nanoparticles were prepared by spontaneous emulsification. The particle size and zeta potential was determined by scanning probe microscopy and Zetasizer, respectively. The prepared particles showed good drug-loading capacity. The in vitro release studies showed that after the initial burst, all the drug-loaded batches provided a continuous and slow release of the drug. Coating of nanoparticles with Polysorbate 80 slightly reduced the drug release from the nanoparticles. Release kinetics studies showed that the release of drug from nanoparticles was diffusion-controlled, and the mechanism of drug release was Fickian. The biodistribution of these particles after intravenous injection in rats showed that of nanoparticles coated with 1% Polysorbate 80 altered the biodistribution pattern of nanoparticles.From the Clinical Editor: In this paper, chitosan nanoparticles are investigated in a pre-clinical study as an optimized delivery system for tacrin, a drug with potential significance in Alzheimer's disease. The preparation showed optimal pharmacokinetic characteristics in a rat model.

Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells

Ratul Kumar Das, Naresh Kasoju, Utpal Bora — 2009-07-17

Abstract: We report a nanoformulation of curcumin with a tripolymeric composite for delivery to cancer cells. The composite nanoparticles (NPs) were prepared by using three biocompatible polymers—alginate (ALG), chitosan (CS), and pluronic—by ionotropic pre-gelation followed by polycationic cross-linking. Pluronic F127 was used to enhance the solubility of curcumin in the ALG-CS NPs. Atomic force and scanning electron microscopic analysis showed that the particles were nearly spherical in shape with an average size of 100 ± 20 nm. Fourier transform–infrared analysis revealed potential interactions among the constituents in the composite NPs. Encapsulation efficiency (%) of curcumin in composite NPs showed considerable increase over ALG-CS NPs without pluronic. The in vitro drug release profile along with release kinetics and mechanism from the composite NPs were studied under simulated physiological conditions for different incubation periods. A cytotoxicity assay showed that composite NPs at a concentration of 500 μg/mL were nontoxic to HeLa cells. Cellular internalization of curcumin-loaded composite NPs was confirmed from green fluorescence inside the HeLa cells. The half-maximal inhibitory concentrations for free curcumin and encapsulated curcumin were found to be 13.28 and 14.34 μM, respectively.From the Clinical Editor: A nanoformulation of curcumin with a tri-component polymeric composite for delivery to cancer cells is reported in this paper. Cellular internalization of curcumin loaded composite nanoparticles was confirmed from green fluorescence inside the HeLa cells.

Cellular uptake and transport of gold nanoparticles incorporated in a liposomal carrier

2009-05-18

Abstract: Recent interest in using gold nanoparticles (Au NPs) for therapy in radiation medicine has motivated development of a liposome-based system to enhance their delivery to cells. In this study, liposomes were demonstrated to perform like a “Trojan Horse” to deliver small (1.4 nm) Au NPs into tumor cells by overcoming the energetically unfavorable endocytosis process for small NPs. The results reveal that the liposomal approach provides a thousand-fold enhancement in the cellular uptake of the small Au NPs. Real-time intracellular tracking of the Au NP–liposomes revealed an average speed of 12.48 ± 3.12 μm/hr for their intracellular transport. Analysis of the time-dependent intracellular spatial distribution of the Au NP–liposomes demonstrated that they reside in lysosomes (final degrading organelles) within 40 minutes of incubation. Knowledge gained in these studies opens the door to pursuing liposomes as a viable strategy for delivery of Au NPs in radiation therapy applications.From the Clinical Editor: Gold nanoparticles (Au NPs) as part of an optimized liposome-based delivery system have been proposed for therapy in radiation medicine. The approach resulted in a thousand-fold enhancement in the cellular uptake of Au NPs compared to conventional delivery methods, with the nanoparticles residing in lysosomes within 40 minutes of incubation.

The effect of poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity

2009-05-18

Abstract: The aim of this work was to investigate the effect of triblock copolymer poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity. Docetaxel-loaded nanoparticles were prepared by oil-in-water emulsion/solvent evaporation technique using biodegradable poly(lactic-co-glycolic acid) (PLGA) with or without addition of poloxamer 188, respectively. The resulting nanoparticles were found to be spherical with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in the docetaxel-resistant MCF-7 TAX30 human breast cancer cell line could be found in comparison with that of PLGA nanoparticles. In addition, the docetaxel-loaded PLGA/poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than that of docetaxel-loaded PLGA nanoparticles and Taxotere (P < .05). In conclusion, the results showed advantages of docetaxel-loaded PLGA nanoparticles incorporated with poloxamer 188 compared with the nanoparticles without incorporation of poloxamer 188 in terms of sustainable release and efficacy in breast cancer chemotherapy.From the Clinical Editor: The effects of poloxamer 188, a triblock copolymer were studied on nanoparticle morphology, size, cancer cell uptake and cytotoxicity. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in resistant human breast cancer cell line was demonstrated, resulting in a significantly higher level of cytotoxicity.

Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer

Anekant Jain, Sanjay K. Jain, N. Ganesh, Jaya Barve, Aadil M. Beg — 2009-05-18

Abstract: Hyaluronic acid–coupled chitosan nanoparticles bearing oxaliplatin (L-OHP) encapsulated in Eudragit S100–coated pellets were developed for effective delivery to colon tumors. The in vitro drug release was investigated using a USP dissolution rate test paddle-type apparatus in different simulated gastrointestinal tract fluids. In therapeutic experiments the pellets of free drug, and hyaluronic acid–coupled and uncoupled chitosan nanoparticles bearing L-OHP were administered orally at the dose of 10 mg L-OHP/kg body weight to tumor-bearing Balb/c mice. In vivo data showed that hyaluronic acid–coupled chitosan nanoparticles delivered 1.99 ± 0.82 and 9.36 ± 1.10 μg of L-OHP/g of tissue in the colon and tumor, respectively after 12 hours, reflecting its targeting potential to the colon and tumor. These drug delivery systems show relatively high local drug concentration in the colonic milieu and colonic tumors with prolonged exposure time, which provides a potential to enhance antitumor efficacy with low systemic toxicity for the treatment of colon cancer.From the Clinical Editor: In this study, a nanoparticle system was developed to deliver oxaliplatin to colorectal tumors. In murine models, the drug delivery system showed relatively high local drug concentration in colonic tumors with prolonged exposure time, which provides a potential for enhanced antitumor efficacy with low systematic toxicity.

Investigation of human keratinocyte cell adhesion using atomic force microscopy

2009-07-21

Abstract: Desmosomal junctions are specialized structures critical to cellular adhesion within epithelial tissues. Disassembly of these junctions is seen consequent to the development of autoantibodies directed at specific desmosomal proteins in blistering skin diseases such as pemphigus. However, many details regarding cell junction activity under normal physiological and disease conditions remain to be elucidated. Because of their complex structure, desmosomal junctions are not well suited to existing techniques for high-resolution three-dimensional structure-function analyses. Here, atomic force microscopy (AFM) is used for detailed characterization and visualization of the cell junctions of human epithelial cells. We demonstrate the ability to image the detailed three-dimensional structure of the cell junction at high magnification. In addition, the effect of specific antibody binding to desmosomal components of the cell junction is studied in longitudinal analyses before and after antibody treatment. We show that antibodies directed against desmoglein 3 (a major component of the desmosomal structural unit, and the major target of autoantibodies in patients with pemphigus vulgaris) are associated with changes at the cell surface of the human keratinocytes and alterations within keratinocyte intercellular adhesion structures, supporting the assertion that cell structures and junctions are modified by antibody binding. The present study indicates that the molecular structure of gap junctions can be more completely analyzed and characterized by AFM, offering a new technological approach to facilitate a better understanding of disease mechanisms and potentially monitor therapeutic strategies in blistering skin diseases.From the Clinical Editor: Disassembly of desmosomal junctions is seen in blistering skin diseases such as Pemphigus. This present study demonstrates that the molecular structure of gap junctions can be more completely analyzed and characterized by atomic force microscopy.

C1 (4C)

2010-02-01

Editorial Board

2010-02-01

Nanomedicine: Nanotechnology, Biology and Medicine

Novel sorbents for removal of gadolinium-based contrast agents in sorbent dialysis and hemoperfusion: preventive approaches to nephrogenic systemic fibrosis

Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery

Dendrimer nanocarriers as versatile vectors in gene delivery

Osteoblasts response to microstructured and nanostructured polyimide film, processed by the use of silica bead microlenses

The role of surface energy of technical polymers in serum protein adsorption and MG-63 cells adhesion

Simultaneous detection of dopamine, ascorbic acid, and uric acid at electrochemically pretreated carbon nanotube biosensors

Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method

Multifunctional magnetic nanoparticles for targeted delivery

Evaluation of cationic liposomes composed of an amino acid–based lipid for neuronal transfection

Measurements of serum C-reactive protein levels in patients with gastric cancer and quantification using silicon nanowire arrays

In vitro proliferating cell models to study cytotoxicity of silica nanowires

Toxic and teratogenic silica nanowires in developing vertebrate embryos

Biogenic synthesis of silver nanoparticles and their synergistic effect with antibiotics: a study against gram-positive and gram-negative bacteria

Comparative evaluation of hepatitis B surface antigen–loaded elastic liposomes and ethosomes for human dendritic cell uptake and immune response

Beta-casein nanovehicles for oral delivery of chemotherapeutic drugs

Porous-wall hollow glass microspheres as novel potential nanocarriers for biomedical applications

Preparation of chitosan nanoparticles containing Naja naja oxiana snake venom

Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine

Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells

Cellular uptake and transport of gold nanoparticles incorporated in a liposomal carrier

The effect of poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity

Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer

Investigation of human keratinocyte cell adhesion using atomic force microscopy

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