Crystallization of Celecoxib in Microemulsion Media

Celecoxib belongs to a new NSAID family specifically inhibiting cyclooxygenase‐2 (COX‐2). The present formulations require high dosage since the transmembrane transport fluctuates and is very difficult to control. We solubilized celecoxib in micelles of nonionic microemulsions and hydrophilic surfactant. The supersaturated solubilized drug was precipitated from the nano‐droplets to form a new solid structure with improved dissolution properties. The selected microemulsion systems loaded with celecoxib were characterized by SAXS, SD‐NMR, viscosity, and electrical conductivity techniques. Precipitation was conducted from W/O as well as from O/W U‐type microemulsions. The crystals obtained by the precipitation were characterized by x‐ray powder scattering, differential scanning calorimetry, FTIR measurements, and microscopic scans.     

Host defense peptides and lipopeptides: modes of action and potential candidates for the treatment of bacterial and fungal infections

Endogenous peptide antibiotics (termed also host-defense or antimicrobial peptides) are known as evolutionarily old components of innate immunity. They were found initially in invertebrates, but later on also in vertebrates, including humans. This secondary, chemical immune system provides organisms with a repertoire of small peptides that act against invasion (for both offensive and defensive purposes) by occasional and obligate pathogens. Each antimicrobial peptide has a broad but not identical spectrum of antimicrobial activity, predominantly against bacteria, providing the host maximum coverage against a rather broad spectrum of microbial organisms. Many of these peptides interact with the target cell membranes and increase their permeability, which results in cell lysis. A second important family includes lipopeptides. They are produced in bacteria and fungi during cultivation on various carbon sources, and possess a strong antifungal activity. Unfortunately, native lipopeptides are non-cell selective and therefore extremely toxic to mammalian cells. Whereas extensive studies have emerged on the requirements for a peptide to be antibacterial, very little is known concerning the parameters that contribute to antifungal activity. This review summarizes recent studies aimed to understand how antimicrobial peptides and lipopeptides select their target cell. This includes a new group of lipopeptides highly potent against pathogenic fungi and yeast. They are composed of inert cationic peptides conjugated to aliphatic acids with different lengths. Deep understanding of the molecular mechanisms underlying the differential cells specificity of these families of host defense molecule is required to meet the challenges imposed by the life-threatening infections.     

Electrospun fibers of functional nanocomposites composed of single‐walled carbon nanotubes,fullerene derivatives,and poly(3‐hexylthiophene)

Electrospinning of fibers composed of poly(3‐hexylthiophene) (P3HT), fullerene derivative, phenyl‐C₆₁‐butyric acid methyl ester (PCBM), and single‐walled carbon nanotubes (SWNT) is reported. While of great promise for photovoltaic applications, morphological control of functional structures is a great challenge for most processing methods. It is demonstrated that the use of a tailor‐made block‐copolymer for dispersion of individual SWNT enables the preparation of stable dispersions of individual tubes that may be further cospun from chloroform solutions with PCBM and P3HT into submicron fibers. The block copolymer used to mediate the colloidal and interfacial interactions in the combined system enables the spinning of centimeters long and uniform fibers. Structural characterization indicates a high degree of ordering and alignment within the fibers and absorption and quenching of the photoluminescence indicate significant interactions among the components. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1263–1268, 2011     

Improved solubilization of Celecoxib in U-type nonionic microemulsions and their structural transitions with progressive aqueous dilution

Celecoxib (clxb) is an important drug for treatment of rheumatoid arthritis and osteoarthritis by specifically inhibiting the enzyme cyclooxygenase-2 (COX-2). Clxb is a type 2 drug characterized by low water solubility (<5 mug/ml) and fast transmembrane transport. The present formulations require high dosage since the transmembrane transport fluctuates and is very difficult to control. Dissolving the drug within an oil phase was not practical since its dissolution was very small and its dispersion in water was impossible. In our recent studies, we learned to construct U-type phase diagrams and to formulate reverse microemulsions (oil-based concentrates) that are progressively and fully dilutable with aqueous phase. In the present study, we solubilized clxb in nanostructures of reverse micelles of U-type nonionic microemulsions that consisted of R(+)-limonene, alcohol, propylene glycol (PG), and hydrophilic surfactant (Tween 60). The solubilization capacity of the drug in these systems is many times higher than in either the oil or the aqueous phase. The clxb solubilized microemulsions are fully diluted with aqueous phase without phase separation. The solubilization capacity decreases as the water content increases. Electrical conductivity, viscosity, and self-diffusion (SD) coefficients of the microemulsion components were measured along a suitable water dilution line. The three major microemulsion regions were detected and the transitions between the W/O to bicontinuous phase and from this phase to the O/W droplets were identified (at 30 and 70 wt% aqueous phase, respectively). From the SD coefficients, it was found that the drug is initially solubilized at the interface of the W/O droplets and there are no significant structural changes. The transition to a bicontinuous phase occurs at the same water content as in the empty (i.e., without drug) system. From the viscosity profiles, we concluded that the drug affects the structure of the bicontinuous phase as reflected in the water content at which the oil-continuous network is destroyed and full inversion occurs (50 vs 55 wt% in the drug-loaded system). Upon further dilution the drug remains solubilized at the interface and is oriented with its hydrophilic part facing the water, and is strongly affects the inversion to O/W droplets. From Small Angle X-ray Scattering (SAXS) measurements we learned that the drug effects the structure of microemulsion droplets and forms "ill-defined structures," probably less spherical. Yet, the overall droplet sizes at the high dilutions did not change very much.