Abstract Complement activation-related pseudoallergy (CARPA) is a hypersensitivity reaction occurring upon intravenous administration of numerous liposomal therapeutics, other nonbiological complex drugs and biologicals. It has a complex molecular and cellular mechanism that involves the production, actions and interactions of numerous vasoactive mediators in blood, including thromboxane A2 (TXA2). This short review focuses on the latter eicosanoid: its role in CARPA, effects underlying some of the symptoms and experimental evidence for its rate-limiting role in pulmonary hypertension in pigs. Animal experiments and recent clinical observations suggest that the cyclooxygenase blocker indomethacin may represent an effective new approach to prevent liposome-induced CARPA, lending clinical relevance to better understand the involvement of TXA2 and other eicosanoids in this adverse immune effect.
In novel fields, it is a necessity to find partners in order to advance. Nanomedicine is a highly interdisciplinary field, and the experts in medicine, nanoscience and targeted medicine, pharmacology, biology, physics, chemistry, biophysics, medicine materials science and certainly also the technicians in engineering and tool providers need to coordinate their skills. This year, from May 7 to 10, the European Foundation for Clinical Nanomedicine celebrates its 10th anniversary. The European and Global Summit for Clinical Nanomedicine and Targeted Medicine will bring together all stakeholders involved in Nanomedicine. CLINAM, as a nonprofit organization, presents this year a program with a strong focus on the route of nanomedicine from basic and enabling sciences to successful clinical applications in targeted and precision medicine and related fields to discuss critically common bottlenecks based on the experience of the past decade by our broad international expert community. Looking back on the last 10 years, we see a substantial development in nanomedicine. Large pharmaceutical companies have now introduced nanomedical departments into their structures. Worldwide more than 2000 start-ups in nanomedicine have been created. Nanomedicine has become a university discipline with worldwide 175 chairs of nanomedicine. A huge amount of obstacles was lowered substantially, and we see that Europe is competitive in the worldwide effort to bring findings in research to applications to the benefit of the patient. Many bridges for international cooperation have their origin in Europe. Over the past decade, the CLINAM Summit evolved to an exquisite and globally unique event where in a debate conference manifold scientific topics are highlighted in short presentations and in depth discussed. CLINAM with its Research Lab led by Prof. Patrick Hunziker and with the realization of now 10 summits has become a pillar of Nanomedicine on an international level. For this year, we again expect participants from more than 35 countries. At CLINAM fundamental scientists, developers and professionals in clinical applications and all persons related to nanomedicine can mutually learn from each other to find better solutions for the medicine of the future. In the last decade, the CLINAM Network has evolved more than 30 cooperation agreements between stakeholders and within them four EU-funded Research projects. A major one is the NanoAthero-Project. The responsible person will highlight the results of the last 4 years in May. This year, the program has changed substantially. It elucidates many new aspects in developing nanomedicine and addresses the hot topics in the field. This year, the CLINAM Summit includes four satellite meetings: – on Arthritis Nanomedicine – on Advancing the Development of Nanomedical Education and Workforce Training – on the State of the Art of the EU-NCL European Characterizations Laboratory, and – the Global Regulatory Authorities and Related Parties Meeting.
Fullerol compounds have potent antioxidant effects on biological systems. Therefore, we examined whether fullerol pretreatment potentiates the brain antioxidant defense system and decreases.-glutamyl transpeptidase (GGT) expression during cerebral ischemia/ reperfusion. Experiments were performed in three groups of rats: sham, control ischemic, and ischemic pretreatment groups. Brain ischemia was induced by 90 min of middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. Rats received fullerol nanoparticles (10 mg/kg, intraperitoneally) 30 min before MCAO. Brain infarction, mRNA levels of GGT, glutathione content, and catalase activity were determined after 24 h reperfusion. MCAO induced extensive lesions in the right hemispheres of the control ischemic group (infarct volume 522 +/- 54 mm3) and a concomitant reduction of the glutathione content (45%) and catalase activity (56%) compared to the sham group. Fullerol in the ischemic pretreatment group significantly decreased the infarct volume (133 +/- 62 mm(3)) and also increased the activity of catalase by 53% compared to control. MCAO additionally increased the mRNA levels of GGT in ischemic hemispheres; however, fullerol considerably decreased the mRNA levels of this gene in the pretreatment group. The findings of the present study indicate that fullerol nanoparticles protect the ischemic brain against ischemia/reperfusion injury through potentiation of the antioxidant defense system and attenuation of GGT expression.
Glucosamine sulfate (GS) has been used orally for the treatment of osteoarthritis (OA). However, it may be susceptible to the liver first pass phenomenon, which greatly affects its bioavailability, in addition to its side effects on the gastrointestinal tract. Alginate nanoparticles (Alg NPs) were investigated as a new drug carrier for transdermal delivery of GS to improve its effectiveness and reduce side effects. GS-Alg NPs were characterized by encapsulation efficiency, NP yield, particle size and surface charge properties. The in vitro release studies of GS and the ex vivo permeability through rat skin were determined using a UV-Vis spectrophotometer. GS-Alg NPs are within the nanometer range of size. High negative surface charge values are obtained and indicate the high suspension stability of the prepared formulation. The in vitro release studies showed that GS is released from Alg NPs in a sustained and prolonged manner. The ex vivo permeability of GS through rat skin is enhanced significantly after encapsulation in the negatively charged Alg NPs. We successfully reported a highly stable nanoparticlulate system using Alg NPs that permits the encapsulation of GS for topical administration, overcoming the disadvantages of oral administration.
Hepatocellular carcinoma (HCC) results in significantly high mortality rates due to its subtle metastatic expressions. Exorbitant costs of anticancer drugs have lead to the concept of repositioning standard drugs for their anticancer potential. One such antialcoholic drug, disulfiram (DSF), has been reported to show significant cytotoxicity (IC50 6 mu M) against hepatocarcinoma cells. Hence, we studied its antimetastatic and proteasome-inhibiting potential to ascertain its efficacy against metastatic hepatocarcinoma. In addition, we also studied the influence of the components of polysorbate 80-stabilised poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) on metastastatic markers and proteasome complexes. A significant reduction in antimigratory assays (0.1 mu M) and gelatin zymography (0.5 mu M) was observed. A Western blot analysis furthermore confirmed the modulation of metastatic markers. Chymotrypsin- like activity was significantly inhibited at 2 mu M of DSF, and in silico docking studies show comparable gliding scores of DSF against standard antimetastatic drugs. Our experiments suggest a significant antimetastatic and proteasome-inhibiting potential of DSF and its loaded NPs. We also infer that polysorbate 80 and PLGA neither show interference with drug behaviour nor inhibit metastasis and proteasome activity, thus behaving as components of a neutral vector. However, they may potentially manipulate the pharmacokinetics of DSF for achieving maximum therapeutic efficacy, in addition to targeted drug delivery.
The use of miconazole nitrate (MN) in the treatment of oropharyngeal candidiasis (OPC) is limited by low drug bioavailability, frequent administration, fungal resistance and toxicity concerns. Lipid nanogel comprising solid lipid nanoparticles (SLNs) incorporated into a gel base could be employed to prolong and target MN to the oromucosal layers, minimizing its associated side effects while enhancing its lethality against resistant Candida albicans. In this study, novel tailor-made oropharyngeal lipid nanogels encapsulating MN were developed and evaluated for improved treatment of OPC. Wide angle X-ray diffractogram analysis revealed the amorphous nature of the lipid matrix, containing beeswax and Phospholipon (R) 90H, used in preparing the SLNs. The SLNs had varied polydispersity indices, good encapsulation efficiency (EE) and mean droplet size of 204.0 +/- 2.9-263.0 +/- 7.1 nm. The developed lipid nanogels were pseudoplastic and possessed suitable mucoadhesive strengths on 'cow-everted' oromucosal tissue, with greater anticandidal properties regarding fungal inhibition than marketed MN formulation (Daktarin (R) oral gel) at equivalent concentration. This study has shown that the activity of MN against oral thrush swab (OTS) of C. albicans was improved by formulation as tailor-made mucoadhesive lipid nanogel, and hence could be exploited as an alternative therapeutic carrier for the effective treatment of OPC.
In this review, we assessed endoscopic imaging using surface-enhanced Raman scattering (SERS). As white-light endoscopy, the current standard for gastrointestinal endoscopy, is limited to morphology, Raman endoscopy using surface-enhanced Raman scattering nanoparticles (SERS endoscopy) was introduced as one of the novel functional modalities. SERS endoscopy has multiplex capability and high sensitivity with low autofluorescence and photobleaching. As a result, multiple molecular characteristics of the lesion can be accurately evaluated in real time while performing endoscopy using SERS probes and appropriate instrumentation. Especially, recently developed dual modality of fluorescence and SERS endoscopy offers easy localization with identification of multiple target molecules. For clinical use of SERS endoscopy in the future, problems of limited field of view and cytotoxicity should be addressed by fusion imaging, topical administration, and non-toxic coating of nanoparticles. We expect SERS endoscopic imaging would be an essential endoscopic technique for diagnosis of cancerous lesions, assessment of resection margins and evaluation of therapeutic responses.
Plasma treatment of silicone surfaces is a useful way of increasing wettability to improve adhesion and a first step in producing various organosilicon thin-film composites. Despite numerous earlier studies, there is no consensus on the effect of plasma treatment nor on the mechanism of the subsequent hydrophobic recovery. X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) were used to study the effect of plasma treatments of polydimethylsiloxane elastomer using four different plasma gases: argon, helium, oxygen, and nitrogen. In each case, the surface was oxidized to produce a thin, wettable, brittle silica-like layer. These surfaces progressively recover their hydrophobicity by diffusion of untreated polymer chains through cracks in the treated layer. Angle-resolved XPS detected the untreated, diffused layer and SEM revealed the common occurrence of cracks in the treated layer, although conditions could be found for each gas where the surface becomes completely wettable by water but is free from cracks.
Superparamagnetic iron oxide nanoparticles (SPIONs) have been identified as a promising material for biomedical applications. These include as contrast agents for medical imaging, drug delivery and/or cancer cell treatment. The nanotoxicological profile of SPIONs has been investigated in different studies and the distribution of SPIONs in the human body has not been fully characterized. The aim of this study was to develop a physiologically- based pharmacokinetic (PBPK) model to predict the pharmacokinetics of SPIONs. The distribution and accumulation of SPIONs in organs were simulated taking into consideration their penetration through capillary walls and their active uptake by specialized macrophages in the liver, spleen and lungs. To estimate the kinetics of SPION uptake, a novel experimental approach using primary macrophages was developed. The murine PBPK model was validated against in vivo pharmacokinetic data, and accurately described accumulation in liver, spleen and lungs. After validation of the murine model, a similar PBPK approach was developed to simulate the distribution of SPIONs in humans. These data demonstrate the utility of PBPK modeling for estimating biodistribution of inorganic nanoparticles and represents an initial platform to provide computational prediction of nanoparticle pharmacokinetics.
This review distinguishes myco-nanotechnology using metallic nanoparticles (meta-NPs) synthesized from edible mushroom matter. Green chemistry approaches were attempted to myco-synthesize meta-NPs (viz., Ag-NP, Au-NP, Se-NP, CdS-NP, Fe-NP, Pa-NP, and ZnS-NP) via different routes using edible mushrooms and have been tested toward 79% biomedical and 21% industrial applications. Biomaterials were used as biofactors to form metallic NPs. In mushroom science, mycomaterials of mushrooms were used at different percentages to mycosynthesize in an ecofriendly/green way; mycomaterials such as crude extracts of basidocarp (53%), mycelial extract or free cell filtrate (28%), in crude form or in purified form such as polysaccharides at different percentages; 9% (especially glucan), -proteins/enzymes (7%) and polysaccharides protein complex (3%) as new research lines. Generally, in this field of mushroom nanoparticles about 84% of mycosynthesized NPs using mushrooms are placed outside the fungal cell (extracellular) and 16% are intracellular in the mushroom hyphae. The knowledge of the performance and influence of meta-NPs in edible mushrooms has developed in the last 10 years. Generally, while Agaricus bisporus was the first to be used in agricultural production Pleurotus spp. has the highest use (38%) in the formation of mushroom NPs. Furthermore, silver nanoparticles (Ag-NPs) have been biosynthesized more often in the fungi kingdom; also, Ag-NPs made up the largest part (64%) in the formation of nanoparticles in mushroom science. Mushroom meta-NPs usually have a spherical shape with sizes from 0.4 nm up to = 300 nm but most of them are < 75 nm. A few recent applications have affected the inhibition of the growth of human pathogenic bacteria by mushroom Ag-NPs in combination with antibiotics. Myco-synthesized meta-NPs using mushrooms, especially Ag-NPs, Au-NPs and Se-NPs, are potent against various cancer cell lines. Thus, these NPs can be used in numerous pharmaceutical drugs. Also, the transport of pharmaceutical drugs and biomaterials using NPs of edible mushrooms is considered a very undervalued and new application in the drug and gene fields. Mushroom metaNPs were investigated for industrial applications such as inorganic NPs, carbon nanotubes and the treatment of waste as nano-biosorbents for the adsorption of toxic metals for cleaning the environment using eco-friendly natural materials for reducing the pollution of the environment in the future.
Graphene oxide (GO) nanomaterials offer a wide range of bioimaging applicability. Almost complete quenching ability of fluorescence by GO and natural interaction of GO with single stranded nucleic acid made GO a useful and intriguing multifunctional nanoplatform both as a biosensor for in vitro microplate diagnostics and as a drug delivery carrier for targeted delivery. GO's large surface area and strong near infrared absorbance contribute to enhancement of a therapeutic effect with abundant loading of drugs for possible photothermal and photodynamic therapy. Bioimaging capability of GO made it a good theranostic tool, while enabling tracing in vivo pharmacokinetics during concurrent treatment. Fluorescence, either signal on or off, Raman and surfaceenhanced Raman scattering (SERs), photoacoustic, and radionuclide imaging modalities can be used for theranostic purposes using GO nanomaterials. In this review, we highlight current applications of GO for bioimaging that are classified into in vitro microplate, in vitro cellular and in vivo bioimaging.
In the last decade, ferromagnetic nanoparticles that are able to be heated under an AMF (alternating magnetic field) have gained considerable interest in the field of nanotechnology. The current study explores the peculiarity of the synthesis and the properties of Fe3O4 and (La, Sr) MnO3 nanoparticles by cryochemical and sol-gel technology, as well the comparative analysis of biological activities of synthesized nanoparticles on different cell lines: the ST cell line (diploid epithelial swine testicular cell line) and the MCF-7S cell line (human breast cancer line). In the study, Fe3O4 and (La, Sr) MnO3 nanoparticles with superparamagnetic properties were synthesized, and magnetic fluids based on them that were efficiently heated when subjected to an AMF (specific loss power -33-37 W/g) were prepared. It was observed that the temperature of magnetic fluids based on Fe3O4 nanoparticles increases linearly to the time of the AMF exposition, whereas for (La, Sr) MnO3 -based fluid, it stabilizes within a given temperature range. It was shown that the nanoparticles of (La, Sr) MnO3, unlike Fe3O4, are characterized by low toxicity, antioxidant activity and the ability to influence on cell-virus interaction on normal cell lines (ST cell line). The possibility of the magnetic fluids obtained in this work to generate heat under the AMF exposition and the lack of side effects make them a potential means for magnetic hyperthermia.
The rationale for the use of nanoparticle formulations to treat cancer is based on the ability of these particles to facilitate selective delivery of drugs to the tumor site, reducing adverse effects and improving therapeutic outcomes. Current clinically approved nanomedicines have managed to reduce adverse effects significantly but the increase in overall survival is modest in many cases. Therefore, even though the goal of a better quality of life for the cancer patients has been achieved in large part, the increase in life expectancy still remains a critical challenge. Abnormalities in the tumor micro-environment prevent homogeneous distribution of nanoparticles to the interior of the tumor, decreasing the efficacy of the drug. Intelligent drug delivery systems offer new hope for overcoming these physiological barriers posed by the tumor and have the potential to provide more effective treatments. This review discusses the barriers to the delivery of nanomedicines to solid tumors, suggests design considerations that could optimize delivery and reviews promising intelligent drug delivery systems that have been developed to date.
The incorporation of radioactive isotope(s) into conventional nanomaterials can bring extra properties which are not possessed by original materials. The resulting radioactive nanomaterials (radio-nanomaterials), with added physical/chemical properties, can be used as important tools for different biomedical applications. In this review, our goal is to provide an up-to-date overview on these applications using radio-nanomaterials. The first section illustrates the utilization of radionanomaterials for understanding of in vivo kinetics of their parent nano-materials. In the second section, we focus on two primary applications of radio-nanomaterials: imaging and therapeutic delivery. With various methods being used to form radio-nanomaterials, they can be used for positron emission tomography (PET), single-photon emission computed tomography (SPECT), and multimodal imaging. Therapeutic isotopes-loading radio-nanomaterials can possess selective killing efficacy of diseased cells (e.g. tumor cells) and can provide promises for certain isotopes which are not able to be used in a conventional manner. The successful and versatile biomedical applications of radio-nanomaterials warrants further investigations of those materials and their optimizations can pave the way to future imaging guidable, personalized treatments in patients.
Many nanomaterials were developed for the anticipated in vivo theranostic use exploiting their unique characteristics as a multifunctional platform. Nevertheless, only a few nanomaterials are under investigation for human use, most of which have not entered clinical trials yet. Radionanomedicine, a convergent discipline of radiotracer technology and use of nanomaterials in vivo, can facilitate clinical nanomedicine because of its advantages of radionuclide imaging and internal radiation therapy. In this review, we focuse on how radionanomedicine would impact profoundly on clinical translation of nanomaterial theranostics. Up-to-date advances and future challenges are critically reviewed regarding the issues of how to radiolabel and engineer radionanomaterials, in vivo behavior tracing of radionanomaterials and then the desired clinical radiation dosimetry. Radiolabeled extracellular vesicles were further discussed as endogenous nanomaterials radiolabeled for possible clinical use.
The growing production and use of nickel (Ni) nanopowders with low biopersistence makes dissolution and accumulation degree in a body an important parameters needed for the risk assessment of nanoparticles. We propose an experimental approach for rapid determination of the dissolution degree of nanoscale (77 nm) and ultrafine (275 nm) Ni particles in synthetic biological solutions. It has been shown that after 2 h of exposure to simulating saliva and lysosomal liquid the dissolution degree of nanoparticles can reach 30 and 60 wt.%, respectively. With decreasing of the particle's size, they are characterized by increased solubility in saliva and the pulmonary tract; and the particles completely dissolve in 24 h. There was an attempt to predict the potential extent of accumulation of nickel compounds in the human body with particles entering the body by saliva or with breathing: with 3.8 times size decrease the probability of nickel accumulation in a body can rise in 3.5 times.
Abstract The aim of this work is to study the kinetics of ultrasound (70 kHz) – using a kinetic model that takes into account cavitation events and drug re-encapsulation upon the cessation of the acoustic field. The simulation allowed the determination of three parameters α, β and λ that define the release and re-encapsulation behavior of this drug delivery system (DDS). The results showed that the drug release increased with increasing power density, as evidenced by the correlation between α and power density. The micelle re-assembly, quantified by the parameter β, also increased with increasing power density. The parameter λ, which is associated with the initial phase of the release process, showed a constant value regardless of the power density. The significance of these results was discussed. Additionally, a comparison between these parameters in folate-targeted and non-targeted micelles showed statistically significant differences for several power densities examined. A better understanding of the kinetics involved in this DDS is very important for the determination of the optimum ultrasound parameters to be used in future in vitro and in vivo experiments.
