Feedback regulated drug delivery vehicles: carbon dioxide responsive cationic hydrogels for antidote release.

A possible approach to handling the harmful side effects of an analgesic overdose, without losing its therapeutic potential, involves feedback regulated delivery of an antidote. For example, overdose of morphine causes hypoventilation, an inadequate ventilation to perform gas exchanges in lungs leading to increased CO2 concentration in the blood. Taking advantage of CO2 as a toxicity marker, a hydrogel-based delivery vehicle containing dimethylamino groups [poly(N,N-dimethylaminoethyl methacrylate) cross-linked by trimethylolpropane trimethacrylate] was designed. Stimulus controlled swelling of these hydrogels in naloxone delivery is discussed. A remarkable control over naloxone release was achieved against the concentration of the biomarker. The overall stimuli response of the gel could be enhanced further by encapsulating carbonic anhydrase, a metalloenzyme known to catalyze the reversible hydration of CO2. Thus, a feedback regulated drug delivery vehicle based on toxicity biomarker strategy was modeled successfully, which has the potential to mitigate risks associated with drug overdose.

Controlled Methodology for Development of a Polydimethylsiloxane-Polytetrafluoroethylene-Based Composite for Enhanced Chemical Resistance: A Structure-Property Relationship Study.

Polydimethylsiloxane (PDMS) polymers are highly appreciated materials that are broadly applied in several industries, from baby bottle nipples to rockets. Momentive researchers are continuously working to understand and expand the scope of PDMS-based materials. Fluorofunctional PDMS has helped the world to apply in specialty applications. Efforts are taken to develop such siloxane-fluoropolymer composite materials with good thermal, solvent, and chemical resistance performances. We leveraged inherently flexible PDMS as the model matrix, whereas polytetrafluoroethylene (PTFE) was used as the additive to impart the functional benefits, offering great value in comparison to the individual polymers. The composites were made at three different mixing temperatures, that is, 0-35 °C, and different loadings of PTFE, that is, 0.5-8% (w/w), were selected as the model condition. A strong dependency of the mixing temperature against the performance attributes of the developed composites was noted. Mechanical and thermal stability of the composites were evaluated along with optical properties. X-ray diffraction demonstrated the change in the crystallite size of the PTFE particles as a function of processing temperature. Compared to the phase II crystallite structure of the PTFE, the fibrils formed in phase IV imparted a better reinforcing capability toward the PDMS matrix. A synergistic balance between higher filler loading and mechanical properties of the composite can be achieved by doping the formulation with short-chain curable PDMS, with 238% increment of tensile strength at 8 wt % PTFE loading when compared to the control sample. The learning was extended to check the applicability of doping such PTFE powder in commercial liquid silicone rubber (LSR). In the window of study, the formulated LSR demonstrated improved mechanical properties with additional functional benefits like resistance toward engine oil and other chemical solvents.

Self-assembly of bile steroid analogues: molecules, fibers, and networks.

Structural and rheological features of a series of molecular hydrogels formed by synthetic bile salt analogues have been scrutinized. Among seven gelators, two are neutral compounds, while the others are cationic systems among which one is a tripodal steroid derivative. Despite the fact that the chemical structures are closely related, the variety of physical characteristics is extremely large in the structures of the connected fibers (either plain cylinders or ribbons), in the dynamical modes for stress relaxation of the associated SAFINs, in the scaling laws of the shear elasticity (typical of either cellular solids or fractal floc-like assemblies), in the micron-scale texture and the distribution of ordered domains (spherulites, crystallites) embedded in a random mesh, in the type of nodal zones (either crystalline-like, fiber entanglements, or bundles), in the evolution of the distribution and morphology of fibers and nodes, and in the sensitivity to added salt. SANS appears to be a suitable technique to infer all geometrical parameters defining the fibers, their interaction modes, and the volume fraction of nodes in a SAFIN. The tripodal system is particularly singular in the series and exhibits viscosity overshoots at the startup of shear flows, an "umbrella-like" molecular packing mode involving three molecules per cross section of fiber, and scattering correlation peaks revealing the ordering and overlap of 1d self-assembled polyelectrolyte species.

Use of novel cationic bile salts in cholesterol crystallization and solubilization in vitro.

Unnatural bile salts have been synthesized with a cationic group at the side chain of natural bile acids. These cationic bile salts aggregate in water and aqueous salt solutions in a manner similar to their natural counterparts. The critical micellar concentrations of the cationic bile salts were measured using a fluorescence method. Cationic bile salts aggregated at a concentration lower than natural deoxycholic acid. Since dihydroxy bile salt micelles are well known for cholesterol dissolution/removal, the dissolution in the cationic micelles has been evaluated. The cationic analogs dissolve approximately 70 mg/dL of cholesterol, which is comparable to taurochenodeoxycholate micelle under identical bile salt concentrations. Cholesterol dissolution in cationic bile salt micelle enhanced upon adding various amounts of PC. Cholesterol crystallization was studied in model bile at various cationic bile salt concentrations. The addition of 5, 15 and 30 mM of the cationic bile salts attenuated the crystallization process, without influencing the crystal observation time or decreasing the final amount of crystals formed. All these effects were comparable to those observed with cholic acid. These findings suggest that cationic bile salts have physico-chemical properties analogous to those of natural anionic bile salts, and thus may have therapeutic potential.

Hydrogels as reaction vessels: acenaphthylene dimerization in hydrogels derived from bile acid analogues.

Many chemical reactions which are otherwise clean often lead to the formation of multiple products. Such products may be formed due to a lack of chemo-, regio- and/or stereoselectivity. For such reactions to be useful, one should be able to control them to yield a single desired product. Of the many approaches used in this context, the use of reaction media with features different from those of isotropic solutions has been very effective. Surfactant micelles have been shown to control the product selectivity in photochemical reactions, but the dynamic nature of the micelles probably results in differential effects on reaction selectivity. In this article we provide the results on photodimerization reactions performed in bile salt gels.

Ammonium lithocholate nanotubes: stability and copper metallization.

Ammonium lithocholate nanotubes (NHLC) have been prepared in alkaline ammonia solutions and exhibited remarkable monodisperse cross-sectional dimensions (external diameter = 52 nm) as shown by cryo-transmission electron microscopy measurements. A classical electroless metallic replication method was used with a single poly(ethylene-imine) PEI layer coating the negatively charged NHLC nanotubes. Short copper rods (external diameter ∼ 80 nm) were observed by scanning electron microscopy that corresponded to the original organic templates. The results obtained in acidic conditions are analyzed in terms of the lifetime of the self-assembled structures and formation of bundles of tubes. Dynamic light scattering measurements and optical observations show that the system in the presence of controlled amounts of hydrochloric acid is stable enough to account for a metallic replication in acidic conditions. An average apparent diffusion coefficient of the organic NHLC assemblies is extracted (∼ 9.8 × 10 nm s) in homogeneous suspensions where bundles have been dispersed by the acidic additions.

Structural relationships in 2,3-bis-n-decyloxyanthracene and 12-hydroxystearic acid molecular gels and aerogels processed in supercritical CO(2).

Supercritical carbon dioxide is used to prepare aerogels of two reference molecular organogelators, 2,3-bis-n-decyloxyanthracene (DDOA) (luminescent molecule) and 12-hydroxystearic acid (HSA). Electron microscopy reveals the fibrillar morphology of the aggregates generated by the protocol. SAXS and SANS measurements show that DDOA aerogels are crystalline materials exhibiting three morphs: (1) arrangements of the crystalline solid (2D p6m), (2) a second hexagonal morph slightly more compact, and (3) a packing specific of the fibers in the gel. Aggregates specific of the aerogel (volume fraction being typically phi approximately 0.60) are developed over larger distances (approximately 1000 A) and bear fewer defaults and residual strains than aggregates in the crystalline and gel phases. Porod, Scherrer and Debye-Bueche analyses of the scattering data have been performed. The first five diffraction peaks show small variations in position and intensity assigned to the variation of the number of fibers and their degree of vicinity within hexagonal bundles of the related SAFIN according to the Oster model. Conclusions are supported by the guidelines offered by the analysis of the situation in HSA aerogels for which the diffraction pattern can be described by two coexisting lamellar-like arrangements. The porosity of the aerogel, as measured by its specific surface extracted from the scattering invariant analysis, is only 1.8 times less than that of the swollen gel and is characteristic of a very porous material.