3D screen printing - An innovative technology for large-scale manufacturing of pharmaceutical dosage forms.

Three-dimensional (3D) screen printing was used to fabricate oral dosage forms of different geometry and size. The paste required as starting material for the 3D screen printing process was designed for delayed release and contained the model drug paracetamol (acetaminophen). A prototype screen printing unit was used to fabricate different tablets in a single production process. The resulting tablets were produced with three different sizes and designed geometries (disk, donut, cuboid, oval and grid). Investigation of size and mass of the individual tablets demonstrated high uniformity within the various groups of tablets. Further characterization of their physical properties, such as breaking force and friability, yielded results comparing favorably to conventionally produced tablets. Finally, drug release tests in artificial gastric media showed paracetamol release to depend on the surface-area-to-volume ratio. In conclusion, the study shows the potential of 3D screen printing to fabricate more complex oral dosage forms in the setting of mass production with high reproducibility.

Substitution pattern controlled aggregation-induced emission in donor-acceptor-donor dyes with one and two propeller-like triphenylamine donors.

We present a comparative study of the spectroscopic properties of the donor-acceptor-donor substituted dyes triphenylamine-allylidenemalononitrile-julolidine (TMJ) and triphenylamine-allylidenemalononitrile-triphenylamine (TMT), bearing one and two propeller-like triphenylamine donor moieties, in solvents of varying polarity and viscosity and in the aggregated and solid state. Our results reveal control of the aggregation-induced spectroscopic changes and the packing motifs of the dye molecules in the solid state by the chemical nature and structure of the second nitrogen-containing donor, i.e., a planar and a rigid julolidine or a twisted triphenyl group. Assuming that the TMT and TMJ aggregates show a comparable arrangement of the molecules to the respective crystals, these different molecular interactions in the solid state are responsible for aggregation induced emission (AIE) in the case of TMT and its absence for TMJ. Moreover, a versatile strategy for the fluorescence enhancement of only weakly emissive AIE dyes is shown, turning these dyes into bright nanoscale fluorescent reporters by using them as stains for preformed polymer particles.

Light-Responsive Size of Self-Assembled Spiropyran-Lysozyme Nanoparticles with Enzymatic Function.

Novel light-responsive nanoassemblies with switchable size and enzymatic activity are built from a protein and a water-soluble spiropyran. Assemblies are created by electrostatic self-assembly in aqueous solution such that the photochromic property of the spiropyran enables light responsiveness. Upon visible light exposure, the aggregate size increases from 200 to 400 nm. The enzyme retains its activity upon aggregation into the assembly, while it decreases through visible light irradiation. Fundamentally, we show how the two different spiropyran isomers, the open-ring merocyanine form and the closed-ring spiropyran form, bind differently to the protein, which triggers the assembly size and use of thermodynamic data to understand the binding process and the size response. Thus, as a proof of concept, a self-assembly driven light-tunable enzyme activity in conjunction with a triggerable assembly size is demonstrated for a model system. The concept bears future potential for various possible biological applications ranging from genetic control over vaccine applications to the detection of certain proteins.

Complexes of the Mycotoxins Citrinin and Ochratoxin A with Aluminum Ions and their Spectroscopic Properties.

The sensitive detection of the mycotoxin citrinin (CIT) utilizing its fluorescence requires approaches to enhance the emission. In this respect, we studied the complexation of CIT and ochratoxin A (OTA) with Al3+ in methanol using absorption and fluorescence spectroscopy. In this context, an isocratic high performance liquid chromatography (HPLC) method using a polymer column and a fluorescence detector was also developed that enables the separation of the metal ion complexes from the free ligands and non-complexed Al3+. CIT and OTA showed distinct changes in their absorption and fluorescence properties upon Al3+-coordination, and the fluorescence of CIT was considerably enhanced. Analysis of the photometrically assessed titration of CIT and OTA with Al3+ using the Job plot method revealed 1:2 and 1:1 stoichiometries for the Al3+ complexes of CIT (Al:CIT) and OTA (Al:OTA), respectively. In the case of CIT, only one ß-diketone moiety participates in Al3+ coordination. These findings can be elegantly exploited for signal amplification and provide the base to reduce the limit of detection for CIT quantification by about an order of magnitude, as revealed by HPLC measurements using a fluorescence detector.

Light-Responsive Shape: From Micrometer-Long Nanocylinders to Compact Particles in Electrostatic Self-Assembly.

A light-triggered shape change of supramolecular nanostructures is achieved through electrostatically self-assembly of linear polyelectrolytes and oppositely charged dyes in aqueous solution: Upon UV-irradiation, 1-µm-long, flexible cylinders with a cross-section of 10 nm convert into ellipsoids of 400 nm × 40 nm. The nano-object shape is encoded in the molecular dye structure.

Water-Soluble Spiropyrans with Inverse Photochromism and Their Photoresponsive Electrostatic Self-Assembly.

A new type of light responsive nanoscale assemblies based on water-soluble spiropyrans is presented. We have synthesized four anionic spiropyrans bearing multiple sulfonate groups and investigated their photochromic behavior in aqueous solution. Depending on the pH, either inverse photochromism (acidic conditions) or normal photochromism (alkaline conditions) is found. Kinetic data for the interconversion of the spiropyran and merocyanine isomers including the subsequent slow hydrolysis have been obtained by UV/Vis spectroscopy. The results show that the spiropyrans undergo hydrolysis in both alkaline and acidic solution, while in the latter the rate is far slower than in the former. This prolonged hydrolytic stability together with the inverse photochromism under acidic conditions makes the sulfonated spiropyrans suitable to build photoresponsive nanostructures with cationic polyelectrolytes. We show how the self-assembly process is driven by electrostatic interactions and how the spiropyrans' photochromic property allows the size control of the supramolecular objects by visible light. The assembly size is characterized by dynamic light scattering and TEM. In addition, UV/Vis and fluorescence spectroscopy and ζ-potential measurements help to explain the size change upon visible light irradiation.

Elucidating Electrostatic Self-Assembly: Molecular Parameters as Key to Thermodynamics and Nanoparticle Shape.

The rational design of supramolecular nanoparticles by self-assembly is a crucial field of research due to the wide applications and the possibility of control through external triggers. Understanding the shape-determining factors is the key for tailoring nanoparticles with desired properties. Here, we show how the thermodynamics of the interaction control the shape of the nanoparticle. We highlight the connection between the molecular structure of building blocks, the interaction strength, and the nanoassembly shape. Nanoparticles are prepared by electrostatic self-assembly of cationic polyelectrolyte dendrimers of different generations and oppositely charged multivalent organic dyes relying on the combination of electrostatic and π-π interactions. Different building blocks have been used to vary interaction strength, geometric constraints, and charge ratio, providing insights into the assembly process. The nanoassembly structure has been characterized using atomic force microscopy, static light scattering, small angle neutron scattering, and UV-vis spectroscopy. We show that the isotropy/anisotropy of the nanoassemblies is related to the dye valency. Isothermal titration calorimetry has been used to investigate both dye-dye and dye-dendrimer interaction. The existence of a threshold value in entropy and enthalpy change separating isotropic and anisotropic shapes for both interactions has been demonstrated. The effects of the dye molecular structure on the interaction thermodynamics and therefore on the nanoparticle structure have been revealed using molecular modeling. The polar surface area of the dye molecule takes a key role in the dye self-interaction. This study opens the possibility for a priori shape determination knowing the building blocks structure and their interactions.

Amphiphilic pentaazamacrocyclic manganese superoxide dismutase mimetics.

Five newly functionalized pentaazamacrocyclic manganese complexes, with variable lengths and amounts of the aliphatic groups (three compounds with one linear chain containing 12, 16, and 22 carbon atoms, i.e., MnL1, MnL2, and MnL3, respectively, as well as two compounds containing two C12 and C16 chains, MnL4 and MnL5, respectively) that are derivatives of the known SOD mimetic, Mn(Me2-Pyane), have been synthesized. These amphiphilic complexes were characterized by the ESI mass spectrometry, potentiometric titrations, light scattering, cyclic voltammetry, and direct stopped-flow determination of their SOD activity at pH 8.1 and 7.4 (in phosphate and HEPES buffers). The formation of supramolecular aggregates that predominantly exist in the solution as a defined micellar/nanostructure assembly, with an average 400 nm size, has been demonstrated for MnL1. The biological effects of the selected complexes (MnL1 and MnL2) on the superoxide level in cytosol and mitochondria have been tested, as well as their effects on the prevention of the lipid peroxidation induced by paraquat. Advantages and disadvantages of the lipophilic pentaazamacrocyclic manganese SOD mimetics in comparison to the corresponding nonsubstituted SOD active complex have been discussed.