Dye doped Nanoparticles in Biomedical Diagnostics

Dye doped nanoparticles are new class of fluorescent labels. They are typically made of silica or polystyrene with tens of thousands of fluorescent dyes entrapped in the pores of its polymer matrix

Nanoparticle-infused-biodegradable-microneedles as drug-delivery systems: preparation and characterisation

For almost two decades, scientists were exploring the use of nanoparticles as drug vesicles capable of protecting their cargo and deliver it to the target site while evading detection by the body. However, their translation to clinical use has been slower than expected. To a large degree, this is due to the difficulty to formulate the nanomaterial into a usable form, in which they retain their unique, size-dependent properties without aggregating into a bulk material. In this work, we describe a simple methodology for synthesising novel biodegradable microneedle systems infused with silica nanoparticles (SiNP). SiNP were doped with small library of model anti-cancer drugs or drug surrogates before being characterised and encapsulated into biodegradable microneedles. Detailed preparation and characterisation methods for both the nanoparticles and the microneedles-infused with nanoparticles is presented here. We demonstrated the distribution of the nanoparticles within the microneedle matrix in a uniform, un-aggregated form, which enabled the release of the nanoparticles in a sustained manner. Formulating nanomaterial into biodegradable, hydrogel-like microneedles showed to be effective in preserving their colloidal properties, whilst simultaneously enabling the transdermal delivery of the nanomaterial into the body. Although the concepts of nanoparticles and biodegradable microneedles have been researched individually, the combination of the two, to the best of our knowledge, offers a new pathway to nanomedicine-related applications

Nanomedicines and microneedles: a guide to their analysis and application

The fast-advancing progress in the research of nanomedicine and microneedles application in the past two decades have suggested that the combination of the two concepts could help to overcome some of the challenges we are facing in healthcare. These include poor patient compliance with medication and the lack of appropriate administration forms that enable the optimal dose to reach the target site. Nanoparticles as drug vesicles can protect their cargo and deliver it to the target site, while evading the body’s defence mechanisms. Unfortunately, despite intense research on nanomedicine in the past 20 years, we still haven’t answered some crucial questions, e.g. about their colloidal stability in solution and their optimal formulation, which makes the translation of this exciting technology from lab bench to a viable product difficult. Dissolvable microneedles could be an effective way to maintain and stabilise nano-sized formulations, whilst enhancing the ability of nanoparticles to penetrate the stratum corneum barrier. Both concepts have been individually investigated fairly well and many analytical techniques for tracking the fate of the nanomaterial with their precious cargo, both in vitro and in vivo, have been established. Yet, to the best of our knowledge, a comprehensive overview of the analytical tools encompassing the concepts of microneedles and nanoparticles with specific and successful examples is missing. In this review, we have attempted to briefly analyse the challenges associated with nanomedicine itself but crucially, we provide an easy-to-navigate scheme of methods, suitable for characterisation and imaging the physico-chemical properties of the material matrix

Expanding the hoogsteen edge of 2'-deoxyguanosine: Consequences for G-quadruplex formation

(Chemical Equation Presented) The synthesis and self-assembling properties of 8-aryl-2'-deoxyguanosine derivatives are described. Our studies suggest that a properly placed acetyl group can increase the stability and specificity of the resulting G-quadruplex supramolecules by enhancing noncovalent interactions such as hydrogen bonds and Ï?-stacking

Self-assembled ionophores based on 8-phenyl-2'-deoxyguanosine analogues

Novel base-modified G-analogues act as self-assembled ionophores for various metal cations. Their extracting efficiency can be modulated by the presence and substitution pattern of a functionalized phenyl group that replaces the H8 in the guanine base

Coumarin-based, switchable fluorescent substrates for enzymatic bacterial detection

Enzymatically-switchable fluorescent substrates, such as the commercially available 4-methyl umbelliferones (4-MU) are used as standard indicators of enzymatic activity for the detection of various microorganisms and pathogens. However, a major disadvantage of 4-MU is its relatively high pKa leading to only partial dissociation of the fluorescent anion under the conditions where the enzymes are most effective (pH 6–6.5). Here we present a method for new, enzymatically-switchable, fluorescent substrates with improved photo-physico/chemical properties. The lead derivative, 4-AAU, shows excellent solubility in aqueous media (0.81?mg/mL) when compared to 4-MU (0.16?mg/mL), significantly improved quantum yield and wider dynamic range of its fluorescence properties. The corresponding bacterial substrate ?-4-AAUG showed superior selectivity in the detection of clinically relevant amounts of E. coli, Enterococcus and K. pneumonia (1 CFU). The fluorescence intensity of ?-4-AAUG was almost 5 times higher than that of the standard, the detection was possible in reasonably short time (? 2.5?h) and with excellent sensitivity

Comprehensive framework for human health risk assessment of nanopesticides

Nanopesticides are not only in an advanced state of research and development but have started to appear on the market. Industry and regulatory agencies need a consolidated and comprehensive framework and guidance for human health risk assessments. In this perspective we develop such a comprehensive framework by exploring two case studies from relevant product types: an active ingredient delivered with a nanocarrier system, and a nanoparticle as an active ingredient. For a nanocarrier system, three entities are tracked during the assessment: the nanocarrier–active ingredient complex, the empty nanocarrier remaining after the complete release of the active ingredient, and the released active ingredient. For the nanoparticle of pure active ingredient, only two entities are relevant: the nanoparticle and the released ions. We suggest important adaptations of the existing pesticide framework to determine the relevant nanopesticide entities and their concentrations for toxicity testing. Depending on the nature of the nanopesticides, additional data requirements, such as those pertaining to durability in biological media and potential for crossing biological barriers, have also been identified. Overall, our framework suggests a tiered approach for human health risk assessment, which is applicable for a range of nanopesticide products to support regulators and industry in making informed decisions on nanopesticide submissions. Brief summaries of suitable methods including references to existing standards (if available) have been included together with an analysis of current knowledge gaps. Our study is an important step towards a harmonized approach accepted by regulatory agencies for assessing nanopesticides

The impact of 8-aryl-and 8-heteroaryl-2'-deoxyguanosine derivatives on G-quadruplex formation

Guanine and G-rich oligonucleotides are known to self-assemble in the presence of a variety of cations to form higher ordered structures known as Gquadruplexes. We have synthesized a library of 8-aryl/heteroaryl-2'-deoxyguanosine derivatives (8ArGs) that are also able to self-assemble into quadruplex structures. We demonstrate that the properties of such quadruplexes can be modulated by the nature of the groups attached to the guanine base. These supramolecules are potentially useful in the development of self-assembled nanodevices

Evaluation of different nonspecific binding blocking agents deposited inside poly(methyl methacrylate) microfluidic flow-cells

Poly(methyl methacrylate) (PMMA) flow-cells containing microwells were deposited with different nonspecific binding blocking agents, namely, bovine serum albumin (BSA), cationic lipid (DOTAP:DOPE) and diethylene glycol dimethyl ether (DEGDME). Water contact angle (WCA) and atomic force microscope (AFM) measurements were carried out to confirm the successful depositions of BSA, DOTAP, and DEGDME onto the PMMA surfaces. Fluorescent intensity measurements were performed to evaluate the degree of nonspecific adsorption of Cy5-labeled anti-IgG proteins onto plain and oxygen plasma-treated (PT) PMMA flow-cells as well as PMMA flow-cells deposited with different above-mentioned blocking agents. We then employed a label-free detection method called total internal reflection ellipsometry (TIRE) to evaluate the stability of the deposited blocking agents inside the PMMA flow-cells. It was found that, while DOTAP:DOPE was the best agent for blocking the nonspecific adsorption, it could be removed from the PMMA surfaces of the flow-cells upon rinsing with phosphate buffered saline (PBS) and later deposited back onto the Au-coated glass sensing substrate of the TIRE. The removal of the blocking agents from PMMA surfaces and their deposition onto the sensing substrate were further manifested by measuring the kinetics and the amount of adsorbed anti-α-hCG proteins. Overall, the dry DEGDME coating by plasma-enhanced chemical vapor deposition (PECVD) showed very good blocking and excellent stability for subsequent assay inside the microwells. Our results could be useful when one considers what blocking agents should be used for PMMA-based microfluidic immunosensor or biosensor devices by looking at both the blocking efficiency and the stability of the blocking agent. © 2011 American Chemical Society