Rectal administration of nanosystems: from drug delivery to diagnostics

The rectal administration of drugs has been an enduring medical practice for either the management of local or systemic conditions. Although mostly regarded as an alternative to other delivery routes, the colorectal mucosa offers an effective pathway for enhanced systemic bioavailability of many active molecules. The fairly stable physicochemical and enzymatic environment of the mucosa and the possibility of partially avoiding the hepatic first-pass effect are some of the potential advantages of rectal drug delivery. At the same time, higher drug levels of drugs can be achieved at colorectal fluids and tissues, which can aid management of local conditions. However, problems with patient acceptability as well as poor and erratic drug absorption may impair efficient use of the rectal drug delivery route. The valuable features of nanotechnology-based systems for mucosal use are well recognized, and their potential as carriers for drug delivery has already been proven for different medical applications/delivery routes. Although still limited, the development of rectal nanomedicines with therapeutic, diagnostic, and prophylactic purposes is steadily emerging and may circumvent some of the problems associated with the more standard delivery approaches. This review discusses the rationale behind the use of nanotechnology-based strategies for rectal drug delivery and provides a critical overview on the various types of nanosystems proposed so far.     

Square Wave Adsorptive Stripping Voltammetry Determination of Chlorpyriphos in Irrigation Agricultural Water

This work describes the electroanalytical determination of Chlorpyriphos pesticide in natural waters using hanging mercury drop electrode allied to square wave adsorptive cathodic stripping voltammetry. The best responses were obtained in Britton?Robinson buffer solutions at pH 2.0, using a frequency of 100 s^–1, a scan increment of 5 mV, a square wave amplitude of 25 mV and an accumulation potential of–0.4 V during 60 s. Therefore, voltammetric responses showed the presence of one well-defined and irreversible reduction peak, at–1.08 V vs. Ag/AgCl/KCl 1.0 M, which involves two electrons in the reduction of carbon?nitrogen bond in the N-heterocyclic system with the participation of protonation equilibrium preceding the electron transfer reaction. Analytical curves were constructed and compared to similar curves performed by gas chromatograph coupled to a selective nitrogen?phosphorus detector, which demonstrates that the proposed methodology is suitable for determining contamination by Chlorpyriphos in complex samples.     

Optimization and characterization of a biosensor assembly for detection of <Emphasis Type="Italic">Salmonella</Emphasis> Typhimurium

The performance of biosensors depends directly on the strategies adopted during their development. In this paper, a fast and sensitive biosensor for Salmonella Typhimurium detection was assembled by using optimization studies in separate stages. The pre-treatment assays, biomolecular immobilization (primary antibody and protein A concentrations), and analytical response (hydroquinone and hydrogen peroxide concentrations) were optimized via voltammetric methods. In the biosensor assembly, a gold surface was modified via the self-assembled monolayer technique (SAM) using cysteamine thiol and protein A for immobilization of anti-Salmonella antibody. The analytical response of the biosensor was obtained through the use of a secondary antibody labeled with a peroxidase enzyme, and the signal was evaluated by applying the chronoamperometry technique. The biosensor was characterized by infrared spectroscopy and cyclic voltammetry. Optimization of protein A and primary antibody concentrations enabled higher analytical signals of 7.5 and 75 mg mL^?1, respectively, to be achieved. The hydroquinone and H₂O₂ concentrations selected were 3 and 300 mM, respectively. The biosensor developed attained a very low detection limit of 10 CFU mL^?1 and a fast response with a final detection time of 125 min. These results indicate that this biosensor is very promising for the food safety and emergency response applications.     

Excited state properties of oligophenyl and oligothienyl swivel cruciforms

A comprehensive study has been undertaken of the electronic spectral and photophysical properties of two oligophenyl (BPH and BPHF) and one oligothienyl (BTF) swivel cruciforms involving measurements of absorption, fluorescence, and phosphorescence spectra, quantum yields of fluorescence (phiF), phosphorescence (phiPh) and triplet formation (phiT), lifetimes of fluorescence (tauF) and of the triplet state (tauT), and quantum yields of singlet oxygen production (phiDelta). From these, all radiative kF and radiationless rate constants, kIC and kISC, have been obtained in solution. The energies of the lowest lying singlet and triplet excited states were also determined at 293 K. Several of the above properties have also been obtained at low temperature and in the solid state (thin films). In general, for the phenyl oligophenyl (BPH) and for the oligothienyl (BTF) compounds, the radiationless decay channels (phiIC+phiISC) are the dominant pathway for the excited-state deactivation, whereas with the fluorene based oligophenyl BPHF the radiative route prevails. In contrast to the general rule found for related oligomers (and polymers) where radiative emission from T1 is absent, with the compounds studied, phosphorescence has been observed for all of the compounds, indicating that this type of functionalization can lead to emissive triplets. Time-resolved fluorescence decays with picosecond resolution revealed multiexponential (bi- and triexponential) decay laws compatible with the existence of more than one species or conformation in the excited state. These results are discussed on the basis of conformational flexibility in the excited state.     

The use of microspectrofluorimetry for the characterization of lake pigments

In this paper, the potential of confocal microfluorescence spectroscopy is explored for the characterization of selected red lake pigments and paints based on alizarin, purpurin and eosin (weak, medium and strong emitters). The anthraquinone pigments have been used since ancient times by artists, and eosin lakes were used by impressionist painters. Reconstructions of artists paints based on 19th century recipes are examined. The paints were made using the lake pigments bound in a range of binding media including gum arabic, collagen, a vinyl emulsion and linseed oil. The acquisition of the spectra is rapid, with high spatial resolution and the data reliable and reproducible. Together with full emission spectra, it was possible to acquire well-resolved excitation spectra for purpurin, alizarin and eosin based colors. The present investigation suggests that micro-emission fluorescence can also be used as a semi-quantitative method for madder lake pigments, enabling the determination of purpurin lake ratio in a mixture of purpurin and alizarin, which is important for provenance studies. The data obtained with microfluorescence emission with those acquired with fiber-optic fluorimetry are compared. The spatial resolution used, 8microm, is appropriate for the analysis of individual pigments particles or aggregates in a paint film. Micro-emission molecular fluorescence proved to be a promising analytical tool to identify the presence of selected red lake pigments combined with a range of binding media.     

Flavylium chromophores as species markers for dragon's blood resins from Dracaena and Daemonorops trees

A simple and rapid liquid chromatographic method with diode-array UV-vis spectrophotometric detection has been developed for the authentication of dragon's blood resins from Dracaena and Daemonorops trees. Using this method it was discovered that the flavylium chromophores, which contribute to the red colour of these resins, differ among the species and could be used as markers to differentiate among species. A study of parameters, such as time of extraction, proportion of MeOH and pH, was undertaken to optimise the extraction of the flavyliums. This method was then used to make extracts from samples of dragon's blood resin obtained from material of known provenance. From the samples analysed 7,6-dihydroxy-5-methoxyflavylium (dracorhodin), 7,4'-dihydroxy-5-methoxyflavylium (dracoflavylium) and 7,4'-dihydroxyflavylium were selected as species markers for Daemonorops spp., Dracaena draco and Dracaena cinnabari, respectively. The chromatograms from these samples were used to build an HPLC-DAD database. The ability to discriminate among species of dragon's blood using the single marker compounds was compared with a principal components analysis of the chromatograms in the HPLC-DAD database. The results from the HPLC-DAD method based on the presence of these flavylium markers was unequivocal. The HPLC-DAD method was subsequently applied to 37 samples of dragon blood resins from the historical samples in the Economic Botany Collection, Royal Botanic Gardens, Kew. The method identified anomalies in how samples in this collection had been labelled. It is clear that the method can be used to evaluate the provenance of samples used in different areas of cultural heritage. It also could be used to monitor the trade of endangered species of dragon's blood and the species being used in complex formulations of traditional Chinese medicine.     

The Crucial Role of Sb2F10 in the Chemical Synthesis of F2

The purely chemical synthesis of fluorine is a spectacular reaction which for more than a century had been believed to be impossible. In 1986, it was finally experimentally achieved, but since then this important reaction has not been further studied and its detailed mechanism had been a mystery. The known thermal stability of MnF₄ casts serious doubts on the originally proposed hypothesis that MnF₄ is thermodynamically unstable and decomposes spontaneously to a lower manganese fluoride and F₂. This apparent discrepancy has now been resolved experimentally and by electronic structure calculations. It is shown that the reductive elimination of F₂ requires a large excess of SbF₅ and occurs in the last reaction step when in the intermediate [SbF₆][MnF₂][Sb₂F₁₁] the addition of one more SbF₅ molecule to the [SbF₆]⁻ anion generates a second tridentate [Sb₂F₁₁]⁻ anion. The two tridentate [Sb₂F₁₁]⁻ anions then provide six fluorine bridges to the Mn atom thereby facilitating the reductive elimination of the two fluorine ligands as F₂.     

On reformulations for the one-warehouse multi-retailer problem

Computing optimal stochastic portfolio execution strategies under an appropriate risk consideration presents many computational challenges. Using Monte Carlo simulations, we investigate an approach based on smoothing and parametric rules to minimize mean and Conditional Value-at-Risk (CVaR) of the execution cost. The proposed approach reduces computational complexity by smoothing the nondifferentiability arising from the simulation discretization and by employing a parametric representation of a stochastic strategy. We further handle constraints using a smoothed exact penalty function. Using the downside risk as an example, we show that the proposed approach can be generalized to other risk measures. In addition, we computationally illustrate the effect of including risk on the stochastic optimal execution strategy.     

Evaluation of thermal stability of enalapril maleate tablets using thermogravimetry and differential scanning calorimetry

Differential scanning calorimetry (DSC) and thermogravimetry (TG) were used in order to evaluate the thermal stability of an enalapril maleate formulation packaged in two types of packaging, polyvinyl chloride/aluminum blister and aluminum strip. Enalapril and the excipients employed in the formulation were also evaluated by TG and DSC. Tablets were analyzed before and after storage in an acclimatized room at 40 °C and relative humidity of 75 % for 90 days. The DSC and TG results were compared with the results of dosage of enalapril and related compounds obtained by high-performance liquid chromatography. These results indicate an occurrence of chemical interaction between enalapril maleate and the excipients during its storage. After storage, it was observed that the enalapril content reduced and the predominant degradation product was diketopiperazine for both types of packaging. The predominance of diketopiperazine could be related to the absence of sodium bicarbonate in the tablets, alkalinizing agent employed in the thermal stabilization of the drug.     

Effects of the interaction between beta-carboline-3-carboxylic acid N-methylamide and polynucleotides on singlet oxygen quantum yield and DNA oxidative damage

The complexation of beta-carboline-3-carboxylic acid N-methylamide (betaCMAM) with the sodium salts of the nucleotides polyadenylic (Poly A), polycytidylic (Poly C), polyguanylic (Poly G), polythymidylic (Poly T) and polyuridylic (Poly U) acids, and with double stranded (dsDNA) and single stranded deoxyribonucleic acids (ssDNA) was studied at pH 4, 6 and 9. Predominant 1:1 complex formation is indicated from Job plots. Association constants were determined using the Benesi-Hildebrand equation. BetaCMAM-sensitized singlet oxygen quantum yields were determined at pH 4, 6 and 9, and the effects on this of adding oligonucleotides, dsDNA and ssDNA were studied at the three pH values. With dsDNA, the effect on betaCMAM triplet state formation was also determined through triplet-triplet transient absorption spectra. To evaluate possible oxidative damage of DNA following singlet oxygen betaCMAM photosensitization, we used thiobarbituric acid-reactivity assays and electrophoretic separation of DNA assays. The results showed no oxidative damage at the level of DNA degradation or strand break.