Journal of interdisciplinary nanomedicine最新文献

One of the most important health concerns in society is the development of nosocomial infections caused by multidrug-resistant pathogens. The purpose of this review is to discuss the issues in current antibiotic therapies and the ongoing progress of developing new strategies for the treatment of ESKAPE pathogen infections, which is acronymized for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. We not only examine the current issues caused by multidrug resistance but we also examine the barrier effects such as biofilm and intracellular localization exploited by these pathogens to avoid antibiotic exposure. Recent innovations in nanomedicine approaches and antibody antibiotic conjugates are reviewed as potential novel approaches for the treatment of bacterial infection, which ultimately may expand the useful life span of current antibiotics.

The wide applications of silver nanoparticles (AgNPs) have raised many concerns worldwide regarding their safety. The few previous studies on the developmental toxicity of AgNPs have been mostly dependent on animal experiments, which are time-consuming and costly. The rapid development of stem cell biology provides a new in vitro alternative to live animal assays for developmental toxicity studies. Here, we assessed the developmental neurotoxicity of AgNPs and Ag ions using a mouse embryonic stem cell (mESC) toxicology model. Our results showed that AgNP and Ag ion treatments did not affect mESC viability or cause accumulation of reactive oxygen species, at concentrations below 1 μg/mL. Conversely, AgNPs and Ag ions perturbed mESC global and neural progenitor cell-specific differentiation processes. In fact, both AgNPs and Ag ions induced the anomalous expression of neural ectoderm marker genes, such as Sox1, Sox3, Map2, NeuroD, Nestin, and Pax6, at concentrations lower than 0.1 μg/mL. Interestingly, AgNP effects manifested at earlier time points as compared with Ag ions. In addition, treatment with Ag ions generated neural progenitor cell abnormal morphology. Overall, our data proved that both AgNPs and Ag ions are toxicants, and their toxic effects are somehow different.

Doxorubicin-induced cardiomyopathy is a clinically prevalent pathology, occurring as a sequelae following chemotherapy for cancer patients. In particular, the “first dose” effect has been particularly challenging, given the heterogeneous and multifactorial nature of this pathophysiology. Here, we describe the development of a physiologically relevant in vitro model for cardiotoxicity testing, using human cells. Primary cardiomyocytes, endothelial, and smooth muscle cells were tri-cultured in 2D, or within nano-fibrous scaffolds in a 3D environment, under dynamic nutrient flow, using the Quasi Vivo® system. State-of-the-art sensor chips were used to detect troponin I levels, 2 h after acute exposure to doxorubicin. We demonstrate a significant improvement in cardiomyocyte viability when grown in a 3D tri-culture environment over a 5-day period and a 10-fold reduction in doxorubicin-induced toxicity. Our tri-culture model can be used as a valuable tool for physiologically relevant assessment of drug-induced cardiotoxicity in vitro.

Nanomedicine is rapidly expanding in the world due to its potential impact in alleviating various critical problems related to health. In this short review, we highlight the developments in nanomedicine in Sri Lanka through the work carried out by various scientists within the country. Potential challenges in the field and obstacles for conversion to clinical products will also be discussed. Even though there are limited contributions in relation to nano-drug carriers, antibacterial agents, and bone prostheses, the research focused on vaccine development, diagnosis, and imaging tools, and high-throughput screening platforms have not been developed. The main emphasis has been on therapeutic applications and anticancer drug delivery. Many hybrid biocompatible materials have been developed for drug delivery applications; however, work has been limited to in vitro studies due to various reasons. These findings can be extended to in vivo studies by strengthening the collaboration between nanotechnologists and health-related scientists, whose contribution at the clinical stages is paramount. Because of the slow pace of infrastructure development and related policies for clinical trials, many discoveries are terminated at the publication stage. Therefore, product development and commercialization are very challenging in the Sri Lankan context. The attraction of venture capitalists, investors, and government commitment represent current challenges for the product development and implementation of nanomedicine applications within the country.

The successful clinical translation of nonviral gene delivery systems has yet to be achieved owing to the biological and technical obstacles to preparing a safe, potent, and cost-effective vector. Hyperbranched polymers, compared with other polymers, have emerged as promising candidates to address gene delivery barriers owing to their relatively simple synthesis and ease of modification, which makes them more feasible for scale-up and manufacturing. Here, we compare hyperbranched poly(amino acids) synthesised by copolymerising histidine and lysine, with hyperbranched polylysine prepared using the well-known “ultrafacile” thermal polycondensation route, to investigate the effects of histidine units on the structure and gene delivery applications of the resultant materials. The conditions of polymerisation were optimised to afford water-soluble hyperbranched polylysine-co-histidine of three different molar ratios with molecular masses varying from 13 to 30 kDa. Spectroscopic, rheological, and thermal analyses indicated that the incorporation of histidine modulated the structure of hyperbranched polylysine to produce a more dendritic polymer with less flexible branches. Experiments to probe gene delivery to A549 cells indicated that all the new hyperbranched polymers were well tolerated, but, surprisingly, the copolymers containing histidine were not more effective in transfecting a luciferase gene than were hyperbranched polylysines synthesised as established literature comparators. We attribute the variations in gene delivery efficacy to the changes induced in polymer architecture by the branching points at histidine residues, and we obtain structure–function information relating histidine content with polymer stiffness, pKa, and ability to form stable polyplexes with DNA. The results are of significance to nanomedicine design as they indicate that addition of histidine as a co-monomer in the synthetic route to hyperbranched polymers not only changes the buffering capacity of the polymer but has significant effects on the overall structure, architecture, and gene delivery efficacy.

Endocytosis is an essential function of cells, with key roles in the internalisation of nutrients, signal molecules and also drugs. Endocytic processes are therefore widely investigated in the context of drug delivery, and inhibitors of endocytic pathways have been used to provide information regarding uptake mechanisms of drug carrier materials. Here we describe studies in which two established inhibitors of clathrin dependent and independent endocytosis, chlorpromazine and methyl-β-cyclodextrin respectively, were employed to probe endocytic pathways of three cell lines chosen to represent tumour-relevant or associated phenotypes: 3 T3 (fibroblasts), HCT 116 (colon cancer) and MGLVA-1 (gastric cancer). For clathrin mediated endocytosis the data highlight that chlorpromazine inhibition of transferrin internalization, via clathrin dependent endocytosis, is cell and time dependent. We also show that inhibition of uptake is transient with a resumption of transferrin internalization after a maximal inhibition period. The same endocytosis inhibitors were used to probe the internalization of 50 and 100 nm carboxylated polystyrene nanoparticles (C-PS-NPs) as model drug delivery carriers. Flow cytometry data indicated that internalisation of C-PS-NPs varied considerably with the incubation time of cells with chlorpromazine or methyl-β-cyclodextrin, and that the effects were also markedly cell-line dependent. These data highlight that the effects of endocytosis inhibitors on the internalisation pathways even of relatively simple nanoparticles are complex and interdependent. We suggest that mechanistic investigations of the endocytic processes which govern practical applications of nanoparticles for diagnostic and therapeutic applications should be considered on a cell, time and concentration basis.

Nanotechnology is a branch of science, which empowers innovation to discover new medical technologies, improving current diagnostic and treatment methods. The scope of nanotechnology focuses mainly on “technology transfer”, in which research aims to facilitate the application of recent nanoscience techniques to conventional medicine development methodologies. Nanomedicine is attractive to researchers who wish to target specific infectious diseases associated with poverty, which is highlighted through the many pertinent examples of recent breakthroughs in nanomedicine. An overview is provided in this study to highlight the barriers and implementation of nanomedicine for various infectious diseases in the African continent. Patient backgrounds provide the greatest of challenges for new technologies in terms of improving bioavailability and dosage. This review points out the current situation of nanomedicine in Africa and explores the possibility of how nanomedicine could improve patient drug regimens and wellbeing.

A nanosuspension (NS) was formulated from the lipophilic molecule cholecalciferol (CL) for enhanced transdermal delivery by embedding this NS into hydrophilic polymer-based dissolving microneedles (DMNs). First, the NS was prepared by sonoprecpitation with different molecular weights of poly (vinyl alcohol) and poly (vinyl pyrrolidone) as stabilizers and using two different solvents for particle size and zeta potential optimization. DMN arrays were then prepared by centrifugation-assisted micromoulding and subsequently dried. Poly (vinyl alcohol) (10 kDa) produced a NS with the lowest particle size ( ̴ 300 nm). These particles yielded DMN with good mechanical properties when combined with aqueous blends of high molecular weight poly (vinyl pyrrolidone) (360 kDa). The particle size remained similar before and after MN preparation, as confirmed by scanning electron microscope. The CL was in the amorphous state in the free particles as well as in the DMN and, hence, no characteristic CL peak was observed in differential scanning calorimetry or X-ray diffraction. DMN arrays were found to be strong enough to bear a 32 N force, showed efficient skin insertion, and penetrated down to the third layer (depth ≈ 375 μm) of the validated skin model Parafilm M®. An ex vivo porcine skin permeation study using Franz diffusion cells compared the permeation of CL from CL-NS-loaded DMN arrays and MN-free CL-NS patches. It was observed that CL-NS-loaded DMN arrays showed significantly higher (498.19 μg ± 89.3 μg) ex vivo skin permeation compared with MN-free CL-NS patches (73.2 μg ± 26.5 μg) over 24 h. This is the first time a NS of a hydrophobic drug has been successfully incorporated into dissolving MN and suggest that NS-containing DMN systems could be a promising strategy for transdermal delivery of hydrophobic drugs.

With current diagnostic methods detection of stage 1 or 2 ovarian cancer using CA125 is possible in only 75% of cases. The ability to detect CA125 at lower concentrations could significantly improve such early stage diagnosis. Here, the use of screen-printed graphene biosensors as a label-free detection platform for CA125 was evaluated. The sensor was fabricated through deposition of a polyaniline layer via electropolymerisation on to a graphene screen-printed electrode. The sensor surface was functionalised with anti-CA125 antibody via covalent cross linking to polyaniline. The fabrication process was characterised through cyclic voltammetry and electrochemical impedance spectroscopy. The limit of detection achieved was 0.923 ng/μL across a dynamic range of 0.92 pg/μL–15.20 ng/μL and represents the most sensitive CA125 detection reported to date. With sensitivity limits at this level, it will now be possible to conduct clinical trials using serum samples collected from early stage ovarian cancer patients and at risk individuals.

Gene therapy depends on the perfect DNA delivery to the nuclear subdomain, where DNA should be orchestrated in a lipid based programmed packaging, like multi-functional envelope type of nano device (MEND) and tetra lamellar multi-functional envelope type of nano device (T-MEND) published elsewhere. In both the packaging system, DNA has to make a complex (core) with a cationic polymer. It is important how about the effect of such a DNA/condenser core inside the programmed-packaging reflects the transgene expression. Here we compared transgene expression of a firefly luciferase gene from both the protaplex (protamine-DNA) and rotaplex (polyrotaxane-DNA), packaged in MENDs. Dendritic cells were transfected with these nanoparticles and transgene expression, cell viability as well as antigen presentations were measured. Transgene expression from the MEND of protaplex was significantly higher in JAWs-II cell (dendritic cell line) and bone marrow dendritic cell. Cell viability and antigen presentations from the protaplex were also prompt and better than that of polyplex, when T-MEND package systems containing protaplex and rotaplex, were compared. Confocal microscopic studies of fluorescently labeled plasmid DNA reflected the evidence of ease decondensation of DNA from the protaplex than that of a rotaplex. Our results suggest that a natural DNA condenser (protamine in protaplex) prefers transgene expression better to those of synthetic polycationic condenser (polyrotaxane in rotaplex).