We report thermal and crystallographic evidence for a previously unknown mannitol hydrate that is formed in the process of freeze-drying. The mannitol hydrate was produced by freeze-drying pure mannitol solutions (1-4% w/v) using the following cycle: (1) equilibration at -5 degreesC for 1 h; (2) freezing at -40 degreesC; (3) primary drying at -10 degreesC for 15 h; and (4) secondary drying at 10 degreesC for 2 h and then 25 degreesC for 5 h. This crystal form was also observed upon freeze-drying in the presence of sorbitol (1% w/v). The mannitol hydrate showed a distinct X-ray powder diffraction pattern, low melting point, and steplike desolvation behavior that is characteristic of crystalline hydrates. The mannitol hydrate was found to be metastable, converting to anhydrous polymorphs of mannitol upon heating and exposure to moisture. The amount of the mannitol hydrate varied significantly from vial to vial, even within the same batch. The formation of mannitol hydrate has several potential consequences: (1) reduced drying rate; (2) redistribution of the residual hydrate water during accelerated storage to the amorphous drug; and (3) vial-to-vial variation of the moisture level.

Due to its strong tendency to crystallize, the glass properties of mannitol cannot be measured directly. However, because mannitol can exist in a fully or partially amorphous state in drug formulations, it is important to determine the glass properties of mannitol. We obtained the glass properties of mannitol by introducing a small amount of sorbitol, an isomer of mannitol, to delay the onset of crystallization. Extrapolation to zero sorbitol concentration yielded the following properties for the mannitol glass: Tg onset = 10.7(o)C, Tg midpoint= 12.6( o)C, Tg end = 18.4 degreesC and DeltaCp = 1.27 J/g/K. In addition, we estimated the following parameters of the mannitol glass from the width of glass transition using the results of Moynihan (J. Am. Ceram. Soc. 1993, 76, 1081) and Angell (J. Phys. Chem. 1994, 98, 13780): DeltaH (at Tg onset) = 103 kcal/mol, D = 11, and T0 = 222 K. The value of T0 is consistent with the Kauzmann temperature TK (236 K) obtained calorimetrically. The properties of the mannitol glass may be useful for predicting the behavior of amorphous mixtures containing mannitol.

We detail the design of hydrophilic metal-coordinating ligands and their use for the effective coating of luminescent quantum dots (QDs). The ligand design exploits the specific, reagent-free nucleophilic addition reaction of amine-modified molecules toward maleic anhydride to introduce several lipoic acid metal anchors, hydrophilic zwitterion moieties, and specific reactive groups along a poly(isobutylene-alt-maleic anhydride) (PIMA) chain. Tunable reactive groups tested in this study include azide, biotin, carboxyl, and amine. Cap exchange with these multilipoic acid ligands via a photochemical ligation strategy yields homogeneous QD dispersions that are colloidally stable over several biologically relevant conditions and for extended periods of time. The zwitterionic coating yields compact nanoparticle size and imparts nonsticky surface properties onto the QDs, preventing protein absorption. The introduction of a controllable number of reactive groups allows conjugation of the QDs to biomolecules via bio-orthogonal coupling chemistries including (1) attachment of the neurotransmitter dopamine to QDs via amine-isothiocyanate reaction to produce a platform capable of probing interactions with cysteine in proteins, based on charge transfer interactions; (2) self-assembly of biotinylated QDs with streptavidin-dye; and (3) ligation of azide-functionalized QDs to cyclooctyne-modified transferrin via copper-free click chemistry, used for intracellular delivery. This ligand design strategy can be used to prepare an array of metal-coordinating ligands adapted for coating other inorganic nanoparticles, including magnetic and plasmonic nanomaterials.

underway to construct hydrogel materials into different shapes such as 3D, [5] 2D, [6] or fiber-like configurations, [7] wherein hydrogel fibers as a novel type of materials cast great impact on our daily life, ranging from smart textile, [8] conductor to functional reinforcements. [9] Compared with 3D and 2D hydrogels, fiber-like hydrogel, also known as 1D hydrogel fiber, always possess smaller cross-sectional areas, [10] which means such thin hydrogel fibers would bear more significant tensile force under the same load, leading to a higher standard on the mechanical properties for engineering 1D hydrogel fibers.With the synergistic effect of covalent and reversible bonds including hydrogen bonds, [11] hydrophobic interactions, [12] ionic bonds, and host-guest interactions, [13] a variety of hydrogel fibers with great mechanical properties have been developed, such as artificial spider silk with twisted core-sheath hydrogel fibers (tensile strength of 895 MPa and strain of 44.3%), [14] ultrastretchable fibers (tensile strength of 5.6 MPa and strain of 1180%), [9] and supramolecular fibers (tensile strength of 193 MPa and strain of 36%). [15] Despite their excellent mechanical properties, those hydrogel fibers are fabricated by manual drawing from the hydrogel, limiting their practical applications where scaled-up manufacture of fibers is required.To satisfy the demand of scaled-up production, the eligible hydrogel fibers are anticipated to be manufactured on a large scale via spinning process, including electrospinning, [16] extrusion spinning, [17] microfluidic or draw-spinning process. [18] For example, Ju et al. developed a hydrogel microfiber based on a continuous draw-spinning process, and the resulting fibers exhibited tensile stress of 1.4 MPa. [19] Song et al. spun a transparent hydrogel fiber possessing tensile stress of 200 kPa. [20] It should be noted that, as for spinning those hydrogel fibers, relatively low crosslinking density is often essential to a spinning solution due to the large deformation required during the spinning process and the requirements for spinning long and uniform hydrogel fibers, [19] which, in turn, leads to unsatisfied mechanical properties of the final spun hydrogel fibers.

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