Synthesis and solution properties of a temperature-responsive PNIPAM–b-PDMS–b-PNIPAM triblock copolymer

In this paper, we report the synthesis and self-assembly of a novel thermoresponsive PNIPAM60–b-PDMS70–b-PNIPAM60 triblock copolymer in aqueous solution. The copolymer used a commercially available precursor modified with an atom transfer radical polymerization (ATRP) initiator to produce an ABA triblock copolymer via ATRP. Small-angle neutron scattering (SANS) was used to shed light on the structures of nanoparticles formed in aqueous solutions of this copolymer at two temperatures, 25 and 40 °C. The poly(dimethylsiloxane) block is very hydrophobic and poly(N-isopropylacrylamide) (PNIPAM) is thermoresponsive. SANS data at 25 °C indicates that the solutions of PNIPAM–b-PDMS–b-PNIPAM copolymers form well-defined aggregates with presumably core–shell structures below cloud point temperature. The scattering curves originating from nanoparticles formed at 40 °C in 100% D2O or 100% H2O were successfully fitted with the Beaucage model describing aggregates with hierarchical structure

Early Treatment with Basal Insulin Glargine in People with Type 2 Diabetes: Lessons from ORIGIN and Other Cardiovascular Trials

Dysglycemia results from a deficit in first-phase insulin secretion compounded by increased insulin insensitivity, exposing beta cells to chronic hyperglycemia and excessive glycemic variability. Initiation of intensive insulin therapy at diagnosis of type 2 diabetes mellitus (T2DM) to achieve normoglycemia has been shown to reverse glucotoxicity, resulting in recovery of residual beta-cell function. The United Kingdom Prospective Diabetes Study (UKPDS) 10-year post-trial follow-up reported reductions in cardiovascular outcomes and all-cause mortality in persons with T2DM who initially received intensive glucose control compared with standard therapy. In the cardiovascular outcome trial, outcome reduction with an initial glargine intervention (ORIGIN), a neutral effect on cardiovascular disease was observed in the population comprising prediabetes and T2DM. Worsening of glycemic control was prevented over the 6.7 year treatment period, with few serious hypoglycemic episodes and only moderate weight gain, with a lesser need for dual or triple oral treatment versus standard care. Several other studies have also highlighted the benefits of early insulin initiation as first-line or add-on therapy to metformin. The decision to introduce basal insulin to metformin must, however be individualized based on a risk-benefit analysis. The landmark ORIGIN trial provides many lessons relating to the concept and application of early insulin therapy for the prevention and safe and effective induction and maintenance of glycemic control in type 2 diabetes

Direct Synthesis of alpha-Azido,omega-hydroxypolyethers by Monomer-Activated Anionic Polymerization

alpha-Azido,omega-hydroxypolyethers were prepared directly by monomer-activated anionic polymerization. The introduction of the azido function in the alpha-position of poly(ethylene oxide), poly(propylene oxide), protected polyglycidol and polyepichlorohydrin was carried out by tetrabutylammonium azide used as initiator. A slight excess of triisobutylaluminum with respect to the ammonium salt ([i-Bu3Al]/[NBu4N3] = 1.5 to 5) was added to trigger the polymerization and get polyethers with controlled molar masses up to 30000 g/mol in a few hours. The terminal hydroxyl function was formed by deactivation of the active polymer ends. The successful and direct preparation of these N-3-functionalized polyethers was proven by NMR spectroscopy, size exclusion chromatography and matrix-assisted laser desorption/ionization time-of-flight characterizations as well as "click" reactions

Synthesis of highly functionalized poly(alkyl cyanoacrylate) nanoparticles by means of click chemistry

A general methodology was proposed to prepare highly functionalized poly(alkyl cyanoacrylate) nanoparticles by means of Huisgen 1,3-dipolar cyclo-addition, the so-called click chemistry. To achieve this goal, different protocols were investigated to obtain azidopoly(ethylene glycol) cyanoacetate of variable molar mass, followed by a Knoevenagel condensation−Michael addition reaction with hexadecyl cyanoacetate to produce a poly[(hexadecyl cyanoacrylate)-co-azidopoly(ethylene glycol) cyanoacrylate] (P(HDCA-co-N3PEGCA)) copolymer, displaying azide functionalities at the extremity of the PEG chains. As a proof of concept, model alkynes were quantitatively coupled either to the P(HDCA-co-N3PEGCA) copolymers in homogeneous medium followed by self-assembly in aqueous solution or directly at the surface of the preformed P(HDCA-co-N3PEGCA) nanoparticles in aqueous dispersed medium, both yielding highly functionalized nanoparticles. This versatile approach, using alkyl cyanoacrylate derivatives, opened the door to ligand-functionalized and biodegradable nanoparticles with “stealth” properties for biomedical applications