We report the ring-opening copolymerization of maleic anhydride with a variety of epoxides catalyzed by a chromium(III) salen complex. Quantitative isomerization of the cis-maleate form of all polymers affords the trans-fumarate analogues. Addition of chain transfer reagents yields low M(n), narrow PDI polymer samples. This method provides access to a range of new unsaturated polyesters with versatile functionality, as well as the first synthesis of high molecular weight poly(propylene fumarate).

Herein we show the formation of a polymer stereocomplex by mixing isotactic, regioregular chains of poly(propylene succinate) synthesized via the copolymerization of cyclic anhydrides and epoxides. The stereocomplex exhibits significantly improved thermal properties in comparison to the enantiopure parent polymers. We demonstrate that stereocomplexation is a route to a new class of semicrystalline polyesters with improved properties, produced from readily accessible starting materials.

Recent developments in polyester synthesis have established several systems based on zinc, chromium, cobalt, and aluminum catalysts for the ring-opening alternating copolymerization of epoxides with cyclic anhydrides. However, to date, regioselective processes for this copolymerization have remained relatively unexplored. Herein we report the development of a highly active, regioselective system for the copolymerization of a variety of terminal epoxides and cyclic anhydrides. Unexpectedly, electron withdrawing substituents on the salen framework resulted in a more redox stable Co(III) species and longer catalyst lifetime. Using enantiopure propylene oxide, we synthesized semicrystalline polyesters via the copolymerization of a range of epoxide/anhydride monomer pairs.

There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn’s and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.

Gold nanoparticles (AuNPs) were incorporated in poly(vinyl alcohol) (PVOH) hydrogel cylinders via diffusion-controlled reductions of tetrachloroauric acid dissolved in the gels using sodium borohydride or ascorbic acid. At certain reagent concentrations, the two reducing agents formed very different hierarchical structured patterns due to their different chemical nature. Sodium borohydride reduction, which likely follows the classical "supersaturation" mechanism, results in the formation of spherical and monodisperse AuNPs of ∼4 nm in diameter located in micrometer-scale stripes in the outer region of the gels. The mobility of the small colloids in the gels allows the formation of alternating particle-rich and particle-depleted stripes. The reaction of sodium borohydride with water and the -OH groups of the gel matrix diminishes its reducing ability over time and limits the AuNP formation to the outer region of the gels. AuNPs of >20 nm in diameter are formed throughout the gel matrices by ascorbic acid reduction, which is consistent with an "organizer" mechanism. Concentric bands of different colors from the outer to the inner regions of the gels;along the direction of ascorbic acid diffusion;are formed as the result of increased particle size and percentage of nonspherical shapes. The lack of stripes on the micrometer scale in the ascorbic acid system is likely due to the impeded mobility of the larger AuNPs. The structural features observed in this study are attributed primarily to the nature of the reaction matrix: reduction is controlled by the diffusion of reducing agents in the hydrogel matrix and the PVOH matrix polymer facilitates the dispersion and stabilization of the AuNPs formed.