Structural Modifications of DPPC Bilayers upon Inclusion of an Antibacterial Cationic Bolaamphiphile.

The emergence of antibiotic-resistant bacterial strains has fostered fundamental research to develop alternative antimicrobial strategies. Among the several systems proposed so far, the association complexes (nanoplexes) formed by transcription factor decoys (TFDs), i.e., short oligonucleotides targeting a crucial bacterial transcription factor, and a bolaform cationic amphiphile, 10,10'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride (12-bis-THA), have demonstrated their potential in vitro and in vivo. The application of these nanoplexes is hampered by a scarce colloidal stability, which can be addressed by including the bolaamphiphile in a liposomal carrier, which is then associated to the TFD. The present study reports an investigation on the effects of 12-bis-THA on the structure of synthetic lipid bilayers to assess the morphology of the mixed assemblies, gain insight into the location of the host within the bilayer, and determine the loading capacity of the carrier. Our results demonstrate that 12-bis-THA promptly inserts within 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC) bilayers, bending its C-12 spacer chain to adopt a conelike shape and shifting the gel-liquid crystalline transition of the chains to lower temperatures. The host liposomal structure is retained for a bolaamphiphile concentration of up to 3.2% mol to DPPC, whereas higher concentrations lead to the destabilization by means of a detergency-like mechanism, with the simultaneous existence of different lamellar-based structures, such as liposomes, bicelles, and rafts, in which DPPC and 12-bis-THA could be present in different molar ratios. Overall, these results shed light on the interaction of the bolaamphiphile with a lipid bilayer and provide valuable insight to better formulate the antimicrobial amphiphile in liposomal carriers to circumvent the colloidal instability of nanoplexes.

A Divalent PAMAM-Based Matrix Metalloproteinase/Carbonic Anhydrase Inhibitor for the Treatment of Dry Eye Syndrome.

Synthetic sulfonamide derivatives are a class of potent matrix metalloproteinase inhibitors (MMPI) that have potential for the treatment of diseases related to uncontrolled expression of these enzymes. The lack of selectivity of the large majority of such inhibitors, leading to the inhibition of MMPs in tissues other than the targeted one, has dramatically reduced the therapeutic interest in MMPIs. The recent development of efficient drug delivery systems that allow the transportation of a selected drug to its site of action has opened the way to new perspectives in the use of MMPIs. Here, a PAMAM-based divalent dendron with two sulfonamidic residues was synthesized. This nanomolar inhibitor binds to the catalytic domain of two MMPs as well as to the transmembrane human carbonic anhydrases (hCAs) XII, which is present in the eye and considered an antiglaucoma target. In the animal model of an experimental dry eye, no occurrence of dotted staining in eyes treated with our inhibitor was observed, indicating no symptoms of corneal desiccation.

Microstructure of colloidal dispersions in the ionic liquid ethylammonium nitrate: influence of the nature of the nanoparticles' counterion.

In order to better identify the key parameters governing colloidal stability in ionic liquids we probe the influence of the nature of the initial counterion of citrate-coated maghemite nanoparticles (NP), with Na(+), Li(+) and ethylammonium (EA(+)) on their dispersions in ethylammonium nitrate (EAN). Chemical analysis shows that sodium and lithium counterions remain at the nanoparticle surface after their transfer from water to EAN, despite their low concentration compared with EA(+). Macroscopically, all suspensions are stable over the range of volume fractions ΦNP tested (∼ 1% to 8%). A microstructural study coupling small angle scattering and magneto-optic birefringence measurements shows that nanoparticles are perfectly dispersed with sodium counterions and interact through weak repulsions. Conversely, small clusters of a few nanoparticles are formed with lithium counterions, with the aggregation number increasing with ΦNP. However, such clusters are fragile; evidence that the attractions responsible for aggregation are of weak amplitude. Suspensions with EA(+) counterions show an intermediate behaviour. Our results demonstrate the determining role of initial counterions of the nanoparticles on the microstructure of colloidal dispersions in ionic liquids and therefore, the essential role of the interfacial zone between the solid and the liquid.

Tuning the colloidal stability in ionic liquids by controlling the nanoparticles/liquid interface.

To shed light on the origin of colloidal stability in ionic liquids,we focus on a model colloidal system (maghemite nanoparticles) in which surface charge and counterion nature can be controlled at will. We thus evidence the crucial role of interfacial features on dispersion quality in a standard ionic liquid, ethylammonium nitrate.

Accuracy of a new partial coherence interferometry analyser for biometric measurements.

AIMS: Precise biometry is an essential preoperative measurement for refractive surgery as well as cataract surgery. A new device based on partial coherence interferometry technology was tested and evaluated for accuracy of measurements. METHODS: In a prospective study 200 eyes of 100 healthy phakic volunteers were examined with a functional prototype of the new ALLEGRO BioGraph (Wavelight AG)/LENSTAR LS 900 (Haag Streit AG) biometer and with the IOLMaster V.5 (Carl Zeiss Meditec AG). As recommended by the manufacturers, repeated measurements were performed with both devices and the results compared using Spearman correlation calculations (WinSTAT). RESULTS: Spearman correlation showed high correlations for axial length and keratometry measurements between the two devices tested. Anterior chamber depth, however, had a lower correlation between the two biometry devices. In addition, the mean values of the anterior chamber depth differed (IOLMaster 3.48 (SD 0.42) mm versus BioGraph/LENSTAR 3.64 (SD 0.26) mm); however, this difference was not statistically different (p>0.05, t test). CONCLUSION: The new biometer provided results that correlated very well with those of the IOLMaster. The ALLEGRO BioGraph/LENSTAR LS 900 is a precise device containing additional features that will be helpful tools for any cataract or refractive surgeon.