Preparation and characterization of beta-lactam antibiotic as Ionic liquids and salts

With the increase of bacterial resistance a large number of therapeutic strategies have been used to fight different kind of infections. In recent years ionic liquids (ILs) have been increasing the popularity and the number of applications. First ionic liquids were used mainly as solvent in organic synthesis, but now they are used in analytical chemistry, separation chemistry and material science among others. Additional to significant developments in their chemical properties and applications, ionic liquids are now bringing unexpected opportunities at the interface of chemistry with the life sciences Ionic liquids (ILs) are currently defined as salts that are composed solely of cations and anions which melt below 100ºC. Our goal in this work is to explore the dual activity of the ionic liquids, due to the presence of two different ions, an ion with bacterial activity as a beta-lactam antibiotic and different kinds of cations. In this work the anions of ILs and salts were derived from three different antibiotics: ampicillin, penicillin and amoxicillin. The cations were derived from substituted ammonium, phosphonium pyridinium and methylimidazolium salts, such as: tetraethyl ammonium, trihexiltetradecilphosphonium, cetylpyridinium, choline (an essential nutrient), 1-ethyl-3-methylimidazolium, and 1-ethanol-3-methyl imidazolium structures. Commercial ammonium and phosponium halogen salts were first transformed into hydroxides. on ionic exchange column (Amberlite IRA-400) in methanol. The prepared hydroxides were then neutralized with beta-lactam antibiotics. After crystallization we obtained pure ILs and salts containing beta-lactam antibiotics. This work presents a novel method for preparation of new salts of antibiotics with low melting point and their characterization.

Ibuprofen-loaded poly(trimethylene carbonate-co-ϵ- caprolactone) electrospun fibres for nerve regeneration

The development of scaffolds that combine the delivery of drugs with the physical support provided by electrospun fibres holds great potential in the field of nerve regeneration. Here it is proposed the incorporation of ibuprofen, a well-known non-steroidal anti-inflammatory drug, in electrospun fibres of the statistical copolymer poly(trimethylene carbonate-co-ε-caprolactone) [P(TMC-CL)] to serve as a drug delivery system to enhance axonal regeneration in the context of a spinal cord lesion, by limiting the inflammatory response. P(TMC-CL) fibres were electrospun from mixtures of dichloromethane (DCM) and dimethylformamide (DMF). The solvent mixture applied influenced fibre morphology, as well as mean fibre diameter, which decreased as the DMF content in solution increased. Ibuprofen-loaded fibres were prepared from P(TMC-CL) solutions containing 5% ibuprofen (w/w of polymer). Increasing drug content to 10% led to jet instability, resulting in the formation of a less homogeneous fibrous mesh. Under the optimized conditions, drug-loading efficiency was above 80%. Confocal Raman mapping showed no preferential distribution of ibuprofen in P(TMC-CL) fibres. Under physiological conditions ibuprofen was released in 24h. The release process being diffusion-dependent for fibres prepared from DCM solutions, in contrast to fibres prepared from DCM-DMF mixtures where burst release occurred. The biological activity of the drug released was demonstrated using human-derived macrophages. The release of prostaglandin E2 to the cell culture medium was reduced when cells were incubated with ibuprofen-loaded P(TMC-CL) fibres, confirming the biological significance of the drug delivery strategy presented. Overall, this study constitutes an important contribution to the design of a P(TMC-CL)-based nerve conduit with anti-inflammatory properties.

Mechanical characterization of polyhydroxyalkanoate and poly (lactic acid) blends

In this work, the mechanical behavior of polyhyroxyalkanoate (PHA)/poly(lactic acid) (PLA) blends is investigated in a wide range of compositions. The mechanical properties can be optimized by varying the PHA contents of the blend. The flexural and tensile properties were estimated by different models: the rule of mixtures, Kerner–Uemura–Takayanagi (KUT) model, Nicolai–Narkis model and Béla–Pukánsky model. This study was aimed at investigating the adhesion between the two material phases. The results anticipate a good adhesion between both phases. Nevertheless, for low levels of incorporation of PHA (up to 30%), where PLA is expectantly the matrix, the experimental data seem to deviate from the perfect adhesion models, suggesting a decrease in the adhesion between both polymeric phases when PHA is the disperse phase. For the tensile modulus, a linear relationship is found, following the rules of mixtures (or a KUT model with perfect adhesion between phases) denoting a good adhesion between the phases over the composition range. The incorporation of PHA in the blend leads to a decrease in the flexural modulus but, at the same time, increases the tensile modulus. The impact energy of the blends varies more than 157% over the entire composition. For blends with PHA weight fraction lower than 50%, the impact strength of the blend is higher than the pure base polymers. The highest synergetic effect is found when the PLA is the matrix and the PHA is the disperse phase for the blend PHA/PLA of 30/70. The second maximum is found for the inverse composition of 70/30. PLA has a heat-deflection temperature (HDT) substantially lower than PHA. For the blends, the HDT increases with the increment in the percentage of the incorporation of PHA. With up to 50% PHA (PLA as matrix), the HDT is practically constant and equal to PLA value. Above this point (PHA matrix), the HDT of the polymer blends increases linearly with the percentage of addition of PHA.

Microencapsulation of herbicide MCPA with native beta-cyclodextrin and its methyl and hydroxypropyl derivatives: An experimental and theoretical investigation

When a pesticide is released into the environment, most of it is lost before it reaches its target. An effective way to reduce environmental losses of pesticides is by using controlled release technology. Microencapsulation becomes a promising technique for the production of controlled release agricultural formulations. In this work, the microencapsulation of chlorophenoxy herbicide MCPA with native b-cyclodextrin and its methyl and hydroxypropyl derivatives was investigated. The phase solubility study showed that both native and b-CD derivatives increased the water solubility of the herbicide and inclusion complexes are formed in a stoichiometric ratio of 1:1. The stability constants describing the extent of formation of the complexes have been determined by phase solubility studies. 1H NMR experiments were also accomplished for the prepared solid systems and the data gathered confirm the formation of the inclusion complexes. 1H NMR data obtained for the MCPA/CDs complexes disclosed noticeable proton shift displacements for OCH2 group and H6 aromatic proton of MCPA provided clear evidence of inclusion complexation process, suggesting that the phenyl moiety of the herbicide was included in the hydrophobic cavity of CDs. Free energy molecular mechanics calculations confirm all these findings. The gathered results can be regarded as an essential step to the development of controlled release agricultural formulations containing herbicide MCPA.

Evolution of Drug Resistance: Insight on TEM -Lactamases Structure and Activity and Beta-Lactam Antibiotics

Extended-spectrum β-lactamases (ESBLs) prevalence was studied in the north of Portugal, among 193 clinical isolates belonging to citizens in a district in the boundaries between this country and Spain from a total of 7529 clinical strains. In the present study we recovered some members of Enterobacteriaceae family, producing ESBL enzymes, including Escherichia coli (67.9%), Klebsiella pneumoniae (30.6%), Klebsiella oxytoca (0.5%), Enterobacter aerogenes (0.5%), and Citrobacter freundii (0.5%). β-lactamases genes blaTEM, blaSHV, and blaCTX-M were screened by polymerase chain reaction (PCR) and sequencing approaches. TEM enzymes were among the most prevalent types (40.9%) followed by CTX-M (37.3%) and SHV (23.3%). Among our sample of 193 ESBL-producing strains 99.0% were resistant to the fourth-generation cephalosporin cefepime. Of the 193 isolates 81.3% presented transferable plasmids harboring genes. Clonal studies were performed by PCR for the enterobacterial repetitive intragenic consensus (ERIC) sequences. This study reports a high diversity of genetic patterns. Ten clusters were found for E. coli isolates and five clusters for K. pneumoniae strains by means of ERIC analysis. In conclusion, in this country, the most prevalent type is still the TEM-type, but CTX-M is growing rapidly.