Biomedical subjects

Carmen Carrillo

Publications and source records attributed to Carmen Carrillo.

3 recordsLinked to original sources

PubMed2004

Effect of binary and ternary polyethyleneglycol and/or beta-cyclodextrin complexes on the photochemical and photosensitizing properties of Naproxen.

The effect of the polyethylene glycol and/or beta-cyclodextrin on the photolability of aqueous solutions of the anti-inflammatory drug Naproxen was studied. In all systems studied, the photodegradation process followed zero-order kinetics, leading to the same photoproducts as in the absence of these additives. Kinetic studies revealed that the presence of polyethylene glycol (PEG) reduced drug photodegradation (phi=0.11 in water and phi=0.045 in the presence of 1% of PEG). By contrast, the binary inclusion complex, Naproxen:beta-CD, did not protect the drug from degradation, phi=0.11. However, the ternary complex, Naproxen:beta-CD:PEG, reduced the efficiency of the photodegradative process to a considerable extent, with phi=0.022 in this system. In all cases the presence of the different additives elicited a change in the photomixture composition, the alcoholic derivative being the major photoproduct formed. Nevertheless, the change in the efficiency of the process and the amount of the photoproducts formed in the different systems were not related with the biodamage produced by the drug. In this sense, the presence of free Naproxen clearly sensitized the photoperoxidation of linoleic acid. The photosensitizing effect decreased as the PEG concentration increased and was completely abolished by both the binary (Naproxen:beta-CD) and ternary (Naproxen:beta-CD:PEG) complexes. In light of these observations, it is possible to speculate that in these systems the prevention of biodamage would be due to a decrease in the contact between the short-lived species generated during Naproxen photodegradation and biological structures, rather than to the nature or amount of the photoproducts.

Kinetics↗

PubMed2003

Ternary naproxen: beta-cyclodextrin:polyethylene glycol complex formation.

The aim of this study was to investigate the effect of the presence of the water-soluble polymer polyethylene glycol (PEG)-MW=35000 g/mol-on the complexation of the phototoxic anti-inflammatory drug naproxen, in its sodium salt form, with beta-cyclodextrin (beta-CD). The data revealed that the polymer does not interact with the uncomplexed naproxen whereas it does with the beta-CD. The presence of different proportions of PEG, in the 0-1% (w/w) range, systematically lowers K(app) of the formation of the naproxen:beta-CD inclusion complex. The reason for the decrease in the complexed drug is the presence of other competing equilibria, the first one is an interaction of the polymer with the beta-CD, which in turn reduces the amount of free CD available for including the naproxen, and the second is the formation of a naproxen:beta-CD:PEG ternary complex with lower affinity than the binary complex. The binding constant of these processes are K(2)=(4.5+/-1.0) x 10(5) M(-1) and K(3)=870+/-19 M(-1), respectively. In addition the presence of the PEG produces an important change in the driving force of the complex formation. In this case the process is enthalpically unfavoured and entropically favoured; these are typical characteristics of processes governed by hydrophobic interactions.

Cyclodextrins↗

PubMed2003

Molecular mechanism of membrane permeabilization by the peptide antibiotic surfactin.

Surfactin, an acidic lipopeptide produced by various strains of Bacillus subtilis, behaves as a very powerful biosurfactant and possesses several other interesting biological activities. This work deals with the molecular mechanism of membrane permeabilization by incorporation of surfactin. The surfactin-induced vesicle contents leakage was monitored by following release of carboxyfluorescein entrapped into unilamellar vesicles made of palmitoyloleoylphosphatidylcholine (POPC). The effect of the addition of cholesterol, dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylethanolamine (POPE) was also checked. It was observed that surfactin was able to induce content leakage at concentrations far below the onset surfactin/lipid ratio for membrane solubilization to occur, which in our system was around 0.92. Electron microscopy showed that vesicles were present after addition of surfactin at a ratio below this value, whereas no vesicles could be observed at ratios above it. Cholesterol and POPE attenuated the membrane-perturbing effect of surfactin, whereas the effect of DPPC was to promote surfactin-induced leakage, indicating that bilayer sensitivity to surfactin increases with the lipid tendency to form lamellar phases, which is in agreement with our previous observation that surfactin destabilizes the inverted-hexagonal structure. Fourier-transform infrared spectroscopy (FTIR) was used to specifically follow the effect of surfactin on different parts of the phospholipid bilayer. The effect on the C=O stretching mode of vibration of POPC indicated a strong dehydration induced by surfactin. On the other hand, the C-H stretching bands showed that the lipopeptide interacts with the phospholipid acyl chains, resulting in considerable membrane fluidization. The reported effects could be useful to explain surfactin-induced 'pore' formation underlying the antibiotic and other important biological actions of this bacterial lipopeptide.

1,2-Dipalmitoylphosphatidylcholine↗