Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

Enhancement of the stability of microporous silica films in non-aqueous solvents at elevated temperature

The effect of Al incorporation and pH adjustment during hydrolysis of the silica precursor on the thermal and structural stability of ordered microporous silica films with a 2D structure is presented. The structural stability of the films was determined from a combination of LA XRD/TEM data with porosity data obtained from ethanol adsorption isotherms. Thermogravimetric analysis and MR data were used to determine the template removal and the thermal stability. Stability of aluminium incorporated silica films has further been examined in several organic solvents with different polarity. A solvent with a higher polarity interacts more strongly with the films; the long-order structure disappeared after exposure to polar solvents. After exposure to non-polar solvents, the pore size uniformity was retained after 48 h. The samples with an Al/Si ratio of 0.007 showed the smallest d-spacing shift after exposure to hexane. The stability was further tested in the hydrogenation of phenylacetylene performed in a batch reactor over 1 wt.% Pd/Si(Al)O-2/Si (Al/Si = 0.007) films at 30 degrees C and 10 bar H-2 with hexane as solvent. No deactivation was observed in two subsequent hydrogenation runs. (C) 2009 Elsevier Inc. All rights reserved.

Acid dissociation of 2,2 '-dipyridylamine in non-aqueous medium when chelated to some Ru(II)N-4 cores

[Ru(2,2'-bipyridine)(2)(Hdpa)](BF4)(2) center dot 2H(2)O (1), [Ru(1,10-phenanthroline)(2)(Hdpa)] (PF6)(2) center dot CH2Cl2 (2) and [Ru(4,4,4',4'-tetramethyl-2,2'- bisoxazoline)(2)(Hdpa)] (PF6)(2) (3) are synthesized where Hdpa is 2,2'-dipyridylamine. The X-ray crystal structures of 1 and 2 have been determined. Hdpa in 1 and 2 is found to bind the metal via the two pyridyl N ends. Comparing the NMR spectra in DMSO-d(6), it is concluded that 3 has a similar structure. The pK(a) values (for the dissociation of the NH proton in Hdpa) of free Hdpa and its complexes are determined in acetonitrile by exploiting molar conductance. These correlate linearly with the chemical shift of the NH proton in the respective entities. (C) 2007 Elsevier B.V. All rights reserved.

Microbial lipases : at the interface of aqueous and non-aqueous media: a review

In recent times, biotechnological applications of microbial lipases in synthesis of many organic molecules have rapidly increased in non-aqueous media. Microbial lipases are the working horses' in biocatalysis and have been extensively studied when their exceptionally high stability in non-aqueous media has been discovered. Stability of lipases in organic solvents makes them commercially feasibile in the enzymatic esterification reactions. Their stability is affected by temperature, reaction medium, water concentration and by the biocatalyst's preparation. An optimization process for ester synthesis from pilot scale to industrial scale in the reaction medium is discussed. The water released during the esterification process can be controlled over a wide range and has a profound effect on the activity of the lipases. Approaches to lipase catalysis like protein engineering, directed evolution and metagenome approach were studied. This review reports the recent development in the field of non-aqueous microbial lipase catalysis and factors controlling the esterification/transesterification processes in organic media.

Rheological Properties of a Sodium Bentonite and Lactose Aqueous Dispersion

Aim of this paper is show the viscosity measure of a sodium bentonite-water-lactose mixture and your rheological behaviour. This analysis showed the formation of tridimensional structure type and formation of stratified silicate/lactose, this occurred due to different concentrations of organic products into mixture and due to a difference of rotation during viscosity measument. Formation of networks is a consequence of the attraction between the silicate layers in water-lactose mixture. In the present work aqueous solutions of lactose with concentration of 7%, 5%, 3%, 1% and 0% (wt %) were used.

Dynamics and Heterogeneity of Pb(II) Binding by SiO2 Nanoparticles in an Aqueous Dispersion

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Iron phthalocyanine in non-aqueous medium forming layer-by-layer films: growth mechanism, molecular architecture and applications

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The electrochemistry of ferrocene in non-aqueous solvents

the electrochemical oxidation of ferrocene on Pt in dimethylformamide, ethanol, propylene carbonate and their aqueous solutions was studied at 25°C. The concentration of the supporting electrolyte, NaClO4, was varied from 0.1 to 0.5 M. The results show that the electrode process may be described as a quasi-reversible one-electron charge transfer, followed by slow decomposition of the oxidized species. © 1987.