Miscibility and Viscoelastic Properties of Acrylic Polyhedral Oligomeric Silsesquioxane-Poly(methyl methacrylate) Blends

Submitted to POLYMER, January 2005We investigate the miscibility of acrylic polyhedral oligomeric silsesquioxanes (POSS) [characteristic size d ≈ 2 nm] and poly(methyl methacrylate)(PMMA) in order to determine the effect of well-dispersed POSS nanoparticles on the thermomechanical properties of PMMA. Two different acrylic POSS species (unmodified and hydrogenated) were blended separately with PMMA at volume fractions up to φ = 0.30. Both POSS species have a plasticizing effect on PMMA by lowering the glass transition temperature Tg and decreasing the melt-state linear viscoelastic moduli measured in small amplitude oscillatory shear flow. The unmodified acrylic-POSS has better miscibility with PMMA than the hydrogenated form, approaching complete miscibility for loadings φ Tg of PMMA, far less than the 17.4°C decrease in the glass transition temperature observed in a blend of 5 vol% dioctyl phthalate (DOP) in PMMA; however, the decrease in the glass transition temperature per added plasticizer molecule is nearly the same in the unmodified acrylic-POSS-PMMA blend compared with the DOP-PMMA blend. Time-temperature superposition (TTS) was applied successfully to the storage and loss moduli data and the resulting shift factors were correlated with a significant increase in free volume of the blends. The fractional free volume f0 = 0.046 for PMMA at T0 = 170°C while for a blend of 5 vol% unmodified acrylic-POSS in PMMA f0 = 0.057, which corresponds to an addition of 0.47 nm3 per added POSS molecule at φ = 0.05. The degree of dispersion was characterized using both wide-angle x-ray diffraction (WAXD) and dynamic mechanical analysis (DMA). Diffraction patterns for both blend systems show clear evidence of phase separation at φ = 0.20 and higher, but no significant phase separation is evident at φ = 0.10 and lower. The storage modulus measured in DMA indicates appreciable phase separation for unmodified acrylic POSS loadings φ = 0.10, while no evidence of phase separation is present in the φ = 0.05 blend in DMA.AFOSR (DURINT program

Thermorheological Properties Near the Glass Transition of Oligomeric Poly(methyl methacrylate) Blended with Acrylic Polyhedral Oligomeric Silsesquioxane Nanocages

Submitted to Rheologica ActaTwo distinct oligomeric species of similar mass and chemical functionality (Mw ≈ 2,000 g/mol), one a linear methyl methacrylate oligomer (radius of gyration Rg ≈ 1.1 nm) and the other a hybrid organic-inorganic polyhedral silsesquioxane nanocage (methacryl-POSS, r ≈ 1.0 nm), were subjected to thermal and rheological tests to compare the behaviors of these geometrically dissimilar molecules over the entire composition range. The glass transition temperatures of the blends varied monotonically between the glass transition temperatures of the pure oligomer (Tg = â47.3°C) and the pure POSS (Tg = â61.0°C). Blends containing high POSS contents (with volume fraction φ_POSS ⥠0.90) exhibited enhanced enthalpy relaxation in DSC measurements, and the degree of enthalpy relaxation was used to calculate the kinetic fragility indices m of the oligomeric MMA (m = 59) and the POSS (m = 74). The temperature dependences of the viscosities were fitted by the free volume-based WLF-VFT framework and a dynamic scaling relation. The calculated values of the fragility from the WLF-VFT fits were similar for the POSS (m = 82) and for the oligomer (m = 76), and the dynamic scaling exponent was similar for the oligomeric MMA and the POSS. Within the range of known fragilities for glass-forming liquids, the temperature dependence of the viscosity was found to be similarly fragile for the two species. The difference in shape of the nanocages and oligomer chains is unimportant in controlling the glass-forming properties of the blends at low volume fractions ( φPOSS < 0.20); however, at higher volume fractions, adjacent POSS cages begin to crowd each other, leading to an increase in the fractional free volume at the glass transition temperature and the observed enhanced enthalpy relaxation in DSC.AFOSR (DURINT Program

Reduction of liver fibrosis by rationally designed macromolecular telmisartan prodrugs

At present there are no drugs for the treatment of chronic liver fibrosis that have been approved by the Food and Drug Administration of the United States. Telmisartan, a small-molecule antihypertensive drug, displays antifibrotic activity, but its clinical use is limited because it causes systemic hypotension. Here, we report the scalable and convergent synthesis of macromolecular telmisartan prodrugs optimized for preferential release in diseased liver tissue. We have optimized the release of active telmisartan in fibrotic liver to be depot-like (that is, a constant therapeutic concentration) through the molecular design of telmisartan brush-arm star polymers, and show that these lead to improved efficacy and to the avoidance of dose-limiting hypotension in both metabolically and chemically induced mouse models of hepatic fibrosis, as determined by histopathology, enzyme levels in the liver, intact-tissue protein markers, hepatocyte necrosis protection and gene-expression analyses. In rats and dogs, the prodrugs are retained long term in liver tissue, and have a well-tolerated safety profile. Our findings support the further development of telmisartan prodrugs that enable infrequent dosing in the treatment of liver fibrosis.National Institutes of Health (U.S.) (Grant 1R01CA220468-01)National Institutes of Health (U.S.) (Fellowship 1F32EB023101