ADO09, a co-formulation of the amylin analogue pramlintide and the insulin analogue A21G, lowers postprandial blood glucose versus insulin lispro in type 1 diabetes.

AIM: To compare the safety, pharmacokinetics and pharmacodynamics of ADO09 with insulin lispro (Lispro) and separate subcutaneous injections of human insulin and pramlintide (Ins&Pram) in 24 subjects with type 1 diabetes. METHODS: At three dosing visits, participants received single doses of ADO09, Ins&Pram or Lispro immediately before eating a standardized mixed meal together with 1 g of acetaminophen, which was used as a surrogate marker to evaluate the kinetics of gastric emptying. Premeal blood glucose was adjusted to 126 mg/dL ± 10% by means of insulin and glucose infusions. The insulin dose was 7.5 U and the pramlintide dose was 45 µg. Blood glucose, glucagon and acetaminophen concentrations were assessed as pharmacodynamic endpoints; insulin and pramlintide concentrations were analysed as pharmacokinetic endpoints, and safety and tolerability were assessed. RESULTS: Compared with Lispro, ADO09 reduced postprandial blood glucose (ppBG) excursions by more than 95% in the first hour postmeal (mean ± SD ∆AUC BG 0-1 h: 1.4 ± 9.9 mg*h/dL vs. 43.5 ± 15.3 mg*h/dL; p < .0001). Maximum ppBG was significantly improved with ADO09 (∆BGmax 87.0 ± 35.5 mg/dL) versus both Lispro (109.2 ± 31.1 mg/dL; p = .0133) and Ins&Pram (109.4 ± 44.3 mg/dL; p = .0357). Gastric emptying with ADO09 was similar to Ins&Pram and significantly slower than with Lispro. All treatments were well tolerated and both adverse events and hypoglycaemic events were rare during the meal test procedure. CONCLUSION: ADO09 was well tolerated and markedly reduced ppBG compared with Lispro. ADO09 formulation was generally similar to the separate administration of insulin and pramlintide, except for a better BG level in the 4-8 h interval postmeal. These positive results warrant further investigations with ADO09.

Segregated and alternately stacked donor/acceptor nanodomains in tubular morphology tailored with zinc porphyrin-C60 amphiphilic dyads: clear geometrical effects on photoconduction.

Amphiphilic zinc porphyrin (P(Zn); electron donor, D)-fullerene (C(60); electron acceptor, A) dyads 2 and 3, bearing an identical hydrophilic wedge with triethylene glycol chains but different linkers between the P(Zn) and C(60) units, self-assemble into nanotubes with essentially different dimensional and geometrical features from one another. The nanotube from dyad 2 with an ester linker consists of a bilayer wall formed with coaxially segregated D and A nanodomains along the tube axis (coaxial D-A heterojunction), thereby displaying explicit photoconductivity with ambipolar carrier transport properties. In contrast, the nanotube from dyad 3 with a rigid arylacetylene linker consists of a monolayer wall with an alternate geometry of D/A stacking, resulting in poor photoconducting outputs. Such a geometrical difference also significantly affects the photovoltaic properties.

Chiroselective assembly of a chiral porphyrin-fullerene dyad: photoconductive nanofiber with a top-class ambipolar charge-carrier mobility.

Upon slow admission of MeOH, the enantiomerically pure form of chiral amphiphilic porphyrin-fullerene dyad 1 in CH(2)Cl(2) self-assembles at 25 degrees C into nanofibers with a built-in donor/acceptor heterojunction, while its racemic form, under identical conditions, self-assembles into submicrometer-sized spheres with a donor/acceptor arrangement essentially different from that in the nanofiber assembly. Although a cast film of the latter hardly shows a photoconducting profile on micrometer-gap electrodes, the former sample clearly displays photoconduction with an ambipolar charge-transporting character. The electron and hole mobilities under zero electric field, as estimated from time-of-flight profiles, are 0.14 and 0.10 cm(2) V(-1) s(-1), respectively, which are comparable to or even better than those reported for top-class organic materials with a donor/acceptor heterojunction.

Block-copolymer-nanowires with nanosized domain segregation and high charge mobilities as stacked p/n heterojunction arrays for repeatable photocurrent switching.

Development of materials for efficient photoenergy conversion is a subject of critical importance in current science and technology. Efficient performance requires well-controlled segregation of electron donor and acceptor moieties, which we have achieved using block copolymers of tetraphenylporphinatozinc(II) (donor) and C(60) fullerene (acceptor) using living ring-opening metathesis polymerization (ROMP). The resulting amphiphilic ROMP block copolymers undergo self-assembly into nanostructured phase-segregated 1-dimensional nanowires with an approximately 5.5 nm periodicity zebra-stripe-like morphology simply by drop-casting solutions of the polymers onto a substrate such as mica or highly oriented pyrolytic graphite (HOPG). Thin films of the self-assembled nanophase-segregated copolymers exhibit high charge carrier mobilities (approximately 0.26 cm(2) V(-1) s(-1)) and electrical conductivities (up to 6.4 x 10(-4) cm(2) V(-1) s(-1)) as well as highly repeatable photocurrent switching with rapid ON/OFF responses upon white light irradiation.

Challenges and breakthroughs in recent research on self-assembly.

The controlled fabrication of nanometer-scale objects is without doubt one of the central issues in current science and technology. However, existing fabrication techniques suffer from several disadvantages including size-restrictions and a general paucity of applicable materials. Because of this, the development of alternative approaches based on supramolecular self-assembly processes is anticipated as a breakthrough methodology. This review article aims to comprehensively summarize the salient aspects of self-assembly through the introduction of the recent challenges and breakthroughs in three categories: (i) types of self-assembly in bulk media; (ii) types of components for self-assembly in bulk media; and (iii) self-assembly at interfaces.

Porphyrin colorimetric indicators in molecular and nano-architectures.

One of the most important outcomes of organic nanotechnologies could be development of well-integrated systems for sensing of particular chemical species. Use of color indicators is an attractive approach to guest reporting. Of the known chromophores, porphyrin and its derivatives are the most widely studied functional chromophores in a diverse range of research fields. In this review, recent developments in colorimetric indicator functions of porphyrin derivatives and related compounds in their molecular and nano-architectures are reviewed according to the classification: (i) rather simple porphyrin derivatives, (ii) porphyrin conjugates, (iii) porphyrins embedded in bulk materials, and (iv) porphyrins in organized films. Porphyrin derivatives with unusual structures, such as expanded and N-confused ones have been used for color indicators in specific cases. Electron and energy transfers in porphyrins conjugated with other functional moieties resulted in dynamic sensing systems including switch-on and switch-off actions. Immobilization of porphyrin color indicators in appropriate matrices is important for practical applications. Use of supramolecular films such as self-assembled monolayers, Langmuir-Blodgett films, and layer-by-layer assemblies as porphyrin nanoarchitectures often offers opportunities for colorimetric outputs based on control of their aggregate structures.

Self-assembly of a pi-electronic amphiphile consisting of a zinc porphyrin-fullerene dyad: formation of micro-vesicles with a high stability.

An amphiphilic zinc porphyrin-fullerene dyad appended with triethyleneglycol chains in aqueous media forms uniformly-sized multilamellar vesicles with a mean diameter of 100 nm that are thermally stable and robust against membrane lysis with surfactants.

Real time self-assembly and reassembly of molecular nanowires of trigeminal amphiphile porphyrins.

Self-assembly and reassembly of high aspect ratio nanowires of trigeminal porphyrins and their manipulation using an atomic force microscope (AFM) is reported.

Polyethylenes bearing a terminal porphyrin group.

An α-[Cu(II)-porphyrin]-polyethylene was synthesized for the first time using copper catalyzed 1,3-dipolar azide-alkyne Huisgen cycloaddition yielding highly colored moiety-substituted polyethylene.

Large scale assembly of ordered donor-acceptor heterojunction molecular wires using the Langmuir-Blodgett technique.

Unidirectionally aligned photoconductive donor-acceptor heterojunction molecular wires spanning over fifty square microns are fabricated using the Langmuir-Blodgett technique.

Effect of anion binding on charge stabilization in a bis-fullerene-oxoporphyrinogen conjugate.

Presence of strongly binding anion, F(-) stabilizes the photo-induced charge-separated states of a bis-fullerene-substituted oxoporphyrinogen due to the large shift in the oxidation potential of the oxoporphyrinogen moiety upon anion binding through hydrogen bonding at its core.