Nanomembrane-driven co-elution and integration of active chemotherapeutic and anti-inflammatory agents

The release of therapeutic drugs from the surface of implantable devices is instrumental for the reduction of medical costs and toxicity associated with systemic administration. In this study we demonstrate the triblock copolymer-mediated deposition and release of multiple therapeutics from a single thin film at the air-water interface via Langmuir–Blodgett deposition. The dual drug elution of dexamethasone (Dex) and doxorubicin hydrochloride (Dox) from the thin film is measured by response in the RAW 264.7 murine macrophage cell line. The integrated hydrophilic and hydrophobic components of the polymer structure allows for the creation of hybrids of the copolymer and the hydrophobic Dex and the hydrophilic Dox. Confirmation of drug release and functionality was demonstrated via suppression of the interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF α) inflammatory cytokines (Dex), as well as TUNEL staining and DNA fragmentation analysis (Dox). The inherent biocompatibility of the copolymeric material is further demonstrated by the lack of inflammation and apoptosis induction in cells grown on the copolymer films. Thus a layer-by-layer anchored deposition of an anti-inflammatory and chemotherapeutic functionalized copolymer film is able to localize drug dosage to the surface of a medical device, all with an innate material thickness of 4 nm per layer

Sol-gel based materials for biomedical applications

Sol-gel chemistry offers a flexible approach to obtaining a diverse range of materials. It allows differing chemistries to be achieved as well as offering the ability to produce a wide range of nano-/micro-structures. The paper commences with a generalized description of the various sol-gel methods available and how these chemistries control the bulk properties of the end products. Following this, a more detailed description of the biomedical areas where sol-gel materials have been explored and found to hold significant potential. One of the interesting fields that has been developed recently relates to hybrid materials that utilize sol-gel chemistry to achieve unusual composite properties. Another intriguing feature of sol-gels is the unusual morphologies that are achievable at the micro- and nano-scale. Subsequently the ability to control pore chemistry at a number of different length scales and geometries has proven to be a fruitful area of exploitation, that provides excellent bioactivity and attracts cellular responses as well as enables the entrapment of biologically active molecules and their controllable release for therapeutic action. The approaches of fine-tuning surface chemistry and the combination with other nanomaterials have also enabled targeting of specific cell and tissue types for drug delivery with imaging capacity

Development of novel nanomedicines for the treatment of non-small cell lung cancer

Lung cancer stands as one of the deadliest diseases, responsible for the most cancer related deaths worldwide. The UK 5-year survival rate of non-small-cell lung cancer (NSCLC), the predominant subtype of lung cancer, stands at 9.5%, highlighting an unmet need for therapeutic intervention. A key issue is the lack of efficacy current chemotherapy regimens have in the clinic. These therapies often suffer from poor tumour targeting, resulting in dissemination throughout the body and inadequate concentrations in the tumour. This causes deleterious side effects contributing to a reduced patient quality of life and ultimately survival. Nanomedicine may serve to overcome the current therapeutic hurdles in treating NSCLC; the use of nanoparticles (NPs) for the delivery of drugs can improve drug targeting to tumours, increasing efficacy and attenuating off-target side effects. NPs can be used to deliver multiple drugs and be made from varying materials such as gold (AuNPs) or polymers. Furthermore, the discovery of oncogenic mutations in genes like EGFR present druggable targets in patients harbouring the appropriate mutations. This can also be taken advantage of using NPs to more directly target tumours and increase therapeutic response. Therefore, the aim of this thesis was to develop novel NP formulations comprised of a chemically modified variant of the tyrosine kinase inhibitor afatinib and gold (Afb-AuNPs) or in combination with vinorelbine as a polymeric dual chemotherapy formulation (Dual-NPs). Drug-bearing NPs were synthesised using a combination of organic chemistry and hydrophobic ion pairing, after which the NPs were extensively characterised to discern their physicochemical properties. We then sought to investigate the in vitro efficacy of NPs. Cell viability studies revealed Afb-AuNPs and Dual-NPs were significantly cytotoxic to various NSCLC cell lines and comparatively nontoxic to noncancerous cells. Moreover, NP formulations were found to significantly inhibit proliferation of A549, H226 and PC-9 cells 3 compared to clinical formulations as determined by electric cell-substrate impedance sensing. The mechanism of uptake in cancer cells was elucidated using fluorescent NPs as a model system and quantified using confocal microscopy. Finally, the in vivo activity of biocompatibility of Dual-NPs was investigated in a physiologically relevant murine model of NSCLC. Taken together, these results highlight the therapeutic potential for NP formulations of chemotherapy.Open Acces

Diverse Applications of Nanomedicine

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic. \ua9 2017 American Chemical Society

Cell Modulation Using Functionalized Nanoparticles

Monolayer functionalized ultra-small gold nanoparticles (AuNPs) provide a versatile platform for applications in cell research. Through rational design of surface ligands, the chemistry of AuNPs are precisely regulated at atomic level. In this dissertation, applications of AuNPs in cell modulation are discussed. The topics are split into two categories. In the first category, functionalized AuNPs are harnessed to generate a robust monolayer on cell culture surface for cell modulation. The proliferation and behavior of different types of cancer cells and normal cells are modulated by tuning the surface ligands of AuNPs. Fate decision of mesenchymal stem cells are also modulated using the same strategy. In the second category, AuNPs are assembled to nanoparticle stabilized capsules (NPSCs) for the delivery of a variety of proteins to cytosol of cells. Using this method, phenotype of cells are rapidly switched without genomic disturbance. In addition, subcellular localization of proteins are also controlled by the combination of subcellular localization signals and NPSC delivery platform. The first non-peptide synthetic nuclear localization signal based on boronate is discovered using NPSC delivery platform as well

Physical Vapor Deposited Biomedical Coatings

The book outlines a series of developments made in the manufacturing of bio-functional layers via Physical Vapour-Deposited (PVD) technologies for application in various areas of healthcare. The scrutinized PVD methods include Radio-Frequency Magnetron Sputtering (RF-MS), Cathodic Arc Evaporation, Pulsed Electron Deposition and its variants, Pulsed Laser Deposition, and Matrix-Assisted Pulsed Laser Evaporation (MAPLE) due to their great promise, especially in dentistry and orthopaedics. These methods have yet to gain traction for industrialization and large-scale application in biomedicine. A new generation of implant coatings can be made available by the (1) incorporation of organic moieties (e.g., proteins, peptides, enzymes) into thin films using innovative methods such as combinatorial MAPLE, (2) direct coupling of therapeutic agents with bioactive glasses or ceramics within substituted or composite layers via RF-MS, or (3) innovation in high-energy deposition methods, such as arc evaporation or pulsed electron beam methods

Sewage sludge heavy metal analysis and agricultural prospects for Fiji

Insoluble residues produced in Waste Water Treatment Plants (WWTP) as by products are known as sewage sludge (SS). Land application of SS, particularly in agricultural lands, is becoming an alternative disposal method in Fiji. However, currently there is no legislative framework governing its use. SS together with its high nutrient and organic matter contents, constitutes some undesired pollutants such as heavy metals, which may limit its extensive use. The focus of this study therefore was to determine the total concentrations of Pb, Zn, Cd, Cu, Cr, Ni and Mn in the SS produced at the Kinoya WWTP (Fiji) and in the non-fertile soil amended with the SS at 20, 40, 60, 80% application rates and in the control (100% Soil). The bioavailable heavy metals were also determined as it depicts the true extent of metal contamination. The treatment mixtures were then used to cultivate cabbage plants in which the total heavy metal uptake was investigated. Total Zn (695.6 mg/kg) was present in the highest amounts in the 100% SS (control), followed by Pb (370.9 mg/kg), Mn (35.0 mg/kg), Cu (65.5 mg/kg), Cr (20.5 mg/kg) and finally Cd (13.5 mg/kg) and hence a similar trend was seen in all treatment mixtures. The potential mobility of sludgeborne heavy metals can be classified as Ni > Cu > Cd > Zn > Mn > Cr > Pb. Total metal uptake in plant leaves and stems showed only the bioavailable metals Cu, Cd, Zn and Mn, with maximum uptake occurring in the leaves. Ni, despite being highly mobile was not detected, due to minute concentrations in the SS treatments. Optimum growth occurred in the 20 and 40% SS treatments. However maximum Cu and Mn uptake occurred in the 40% SS treatment thereby making the 20% treatment the most feasible. Furthermore the total and bioavailable metal concentrations observed were within the safe and permitted limits of the EEC and USEPA legislations

Next generation transduction pathways for nano-bio-chip array platforms

textIn the following work, nanoparticle quantum dot (QD) fluorophores have been exploited to measure biologically relevant analytes via a miniaturized sensor ensemble to provide key diagnostic and prognostic information in a rapid, yet sensitive manner—data essential for effective treatment of many diseases including HIV/AIDS and cancer. At the heart of this “nano-bio-chip” (NBC) sensor is a modular chemical/cellular processing unit consisting of either a polycarbonate membrane filter for cell-based assays, or an agarose bead array for detection of biomarkers in serum or saliva. Two applications of the NBC sensor system are described herein, both exhibiting excellent correlation to reference methods ((R² above 0.94), with analysis times under 30 minutes and sample volumes below 50 [mu]L. First, the NBC sensor was employed for the sequestration and enumeration of T lymphocytes, cells specifically targeted by HIV, from whole blood samples. Several different conjugation methods linking QDs to recognition biomolecules were extensively characterized by biological and optical methods, with a thiol-linked secondary antibody labeling scheme yielding intense, specific signal. Using this technique, the photostability of QDs was exploited, as was the ability to simultaneously visualize different color QDs via a single light pathway, effectively reducing optical requirements by half. Further, T-cell counts were observed well below the 200/[mu]L discriminator between HIV and AIDS and across the common testing region, demonstrating the first reported example of cell counting via QDs in an enclosed, disposable device. Next, multiplexed bead-based detection of cancer protein biomarkers CEA, Her-2/Neu, and CA125 in serum and saliva was examined using a sandwich immunoassay with detecting antibodies covalently bound to QDs. This nano-based signal was amplified 30 times versus molecular fluorophores and cross talk in multiplexed experiments was less than 5%. In addition, molecular-level tuning of recognition elements (size, concentration) and agarose porosity resulted in NBC limits of detection two orders of magnitude lower than ELISA, values competitive with the most sensitive methods yet reported (0.021 ng/mL CEA). Taken together, these efforts serve to establish the valuable role of QDs in miniaturized diagnostic devices with potential for delivering biomedical information rapidly, reliably, and robustly.Chemistry and Biochemistr