Protein delivery based on uncoated and chitosan-coated mesoporous silicon microparticles

Mesoporous silicon is a biocompatible, biodegradable material that is receiving increased attention for pharmaceutical applications due to its extensive specific surface. This feature enables to load a variety of drugs in mesoporous silicon devices by simple adsorption-based procedures. In this work, we have addressed the fabrication and characterization of two new mesoporous silicon devices prepared by electrochemistry and intended for protein delivery, namely: (i) mesoporous silicon microparticles and (ii) chitosan-coated mesoporous silicon microparticles. Both carriers were investigated for their capacity to load a therapeutic protein (insulin) and a model antigen (bovine serum albumin) by adsorption. Our results show that mesoporous silicon microparticles prepared by electrochemical methods present moderate affinity for insulin and high affinity for albumin. However, mesoporous silicon presents an extensive capacity to load both proteins, leading to systems were protein could represent the major mass fraction of the formulation. The possibility to form a chitosan coating on the microparticles surface was confirmed both qualitatively by atomic force microscopy and quantitatively by a colorimetric method. Mesoporous silicon microparticles with mean pore size of 35 nm released the loaded insulin quickly, but not instantaneously. This profile could be slowed to a certain extent by the chitosan coating modification. With their high protein loading, their capacity to provide a controlled release of insulin over a period of 60-90 min, and the potential mucoadhesive effect of the chitosan coating, these composite devices comprise several features that render them interesting candidates as transmucosal protein delivery systems.     

Synthesis and photophysics of silicon phthalocyanine-perylenebisimide triads connected through rigid and flexible bridges

Three new bisperylenebisimide-silicon phthalocyanine triads [(PBI)(2)-SiPcs 1, 2, and 3] connected with either rigid or flexible bridges were synthesized and characterized. A new synthetic approach to connect SiPc and PBI moieties through click chemistry produced triad 3 with an 80% yield. In (PBI)(2)-SiPc 1, PBI and SiPc are orthogonal and were connected with a rigid connector; triads 2 and 3 bear flexible aliphatic bridges, resulting in a tilted (2) or nearly parallel arrangement (3) of PBI and SiPc. Photoinduced intramolecular processes in these (PBI)(2)-SiPcs were studied and the results are compared with those of the reference compounds SiPc-ref and PBI-ref. The occurrence of electron-transfer processes between the SiPc and PBI units was confirmed by time-resolved emission and transient absorption techniques. Charge-separated (CS) states with lifetimes of 0.91, 1.3 and 2.0 ns for triads 1, 2, and 3, respectively, were detected using femtosecond laser flash photolysis. Upon the addition of Mg(ClO(4))(2), an increase in the lifetime of the CS states to 59, 110 and 200 μs was observed for triads (PBI)(2)-SiPcs 1, 2, and 3, respectively. The energy of the CS state (SiPc(·+)-PDI(·-)/Mg(2+)) is lower than the energy of both silicon phthalocyanine ((3)SiPc*-PDI) and perylenebisimide (SiPc-(3)PDI*) triplet excited states, which decelerates the metal ion-decoupled electron-transfer process for charge recombination to the ground state, thus increasing the lifetime of the CS state. The photophysics of the three triads demonstrate the importance of the rigidity of the spacer and the orientation between donor and acceptor units.     

Three-dimensional open-frameworks based on Ln(III) ions and open-/closed-shell PTM ligands: synthesis, structure, luminescence, and magnetic properties

A series of isostructural open-framework coordination polymers formulated as [Ln(dmf)(3)(ptmtc)] (Ln = Sm (1), Eu (2), Gd (3), Tb (4), Dy (5); PTMTC = polychlorotriphenylmethyl tricarboxylate) and [Ln(dmf)(2)H(2)O(αH-ptmtc)] (Ln = Sm (1'), Eu (2'), Gd (3'), Tb (4'), Dy (5')) have been obtained by treating Ln(III) ions with PTMTC ligands with a radical (PTMTC(3-)) or a closed-shell character (αH-PTMTC(3-)). X-ray diffraction analyses reveal that these coordination polymers possess 3D architectures that combine large channels and fairly rare lattice complex T connectivity. In addition, these compounds show selective framework dynamic sorption properties. For both classes of ligands, the ability to act as an antenna in Ln sensitization processes has been investigated. No luminescence was observed for compounds 1-5, and 3' because of the PTMTC(3-) ligand and/or Gd(III) ion characteristics. Conversely, photoluminescence measurements show that 1', 2', 4', and 5' emit dark orange, red, green, and dark cyan metal-centered luminescence. The magnetic properties of all of these compounds have been investigated. The nature of the {Ln-radical} exchange interaction in these compounds has been assessed by comparing the behavior of the radical-based coordination polymers 1-5 with those of the compounds with the diamagnetic ligand set. While antiferromagnetic {Sm-radical} interactions are found in 1, ferromagnetic {Ln-radical} interactions propagate in the 3D architectures of 3, 4, and 5 (Ln = Gd, Tb, and Dy, respectively). This procedure also provided access to information on the {Ln-Ln} exchange existing in these magnetic systems.     

Effects of the net charge on abundance and stability of supramolecular surfactant aggregates in gas phase

Self-assembling of amphiphilic molecules under electrospray ionization (ESI) conditions is characterized by quite unexpected phenomenology. The noticeable differences with respect to the condensed phase are attributable to the absence of the surfactant-solvent interactions, the presence of net charge in the aggregates, and the strong deviation from equilibrium conditions. Aiming to investigate the effects of the net charge on abundance and stability of supramolecular surfactant aggregates, positively and negatively charged aggregates of sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and sodium methane sulfonate (MetS), butane sulfonate (ButS) and octane sulfonate (OctS) have been studied by ESI mass spectrometry, energy resolved mass spectrometry and density functional theory calculations. The negatively charged aggregates are found to be less stable than their positive counterparts. The results are consistent with a self-assembling pattern dominated by electrostatic interactions involving the counterions and head groups of the investigated amphiphilic compounds while the alkyl chains point outwards, protecting the aggregates from unlimited growth processes.     

Thiolato gold(I) complexes containing water-soluble phosphane ligands: a characterization of their chemical and biological properties

A series of thiolate gold(I) derivatives bearing water soluble phosphanes--namely sodium triphenylphosphane monosulfonate (TPPMS), sodium triphenylphosphane trisulfonate (TPPTS), 1,3,5-triaza-7-phosphaadamantane (PTA) and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA)--is reported and the compounds studied for their luminescence properties in the solid state. Two of these derivatives, [Au(SMe(2)pyrim)(PTA)] and [Au(SBenzoxazole)(DAPTA)], are also structurally characterized by X-ray diffraction analysis. Strong antiproliferative effects are observed for most of the compounds in the human ovarian carcinoma cell lines (A2780/S) and its cisplatin-resistant variant (A2780/R), which depend on both the type of thiolate and phosphane ligands. ICP-MS studies were also performed to evaluate the influence of the gold uptake on the cytotoxic potency of the compounds.     

Structure, solution chemistry, antiproliferative actions and protein binding properties of non-conventional platinum(II) compounds with sulfur and phosphorus donors

Twelve Pt(II) complexes with cis-PtP(2)S(2) pharmacophores (where P(2) refers to two monodentate or one bidentate phosphane ligand and S(2) is a dithiolato ligand) were prepared, characterized and evaluated as potential antiproliferative agents. The various compounds were first studied from the structural point of view; afterward, their solubility properties as well as their solution behaviour were analyzed in detail. Antiproliferative properties were specifically evaluated against A2780 human ovarian carcinoma cells, either resistant or sensitive to cisplatin. For comparison purposes similar studies were carried out on four parent cis-dichloro bisphosphane Pt(II)complexes. On the whole, the cis-PtP(2)S(2) compounds displayed significant antiproliferative properties while the cis-PtP(2)Cl(2) (cis-dichloro bisphosphane Pt(II)) compounds revealed quite poor biological performances. To gain further insight into the molecular mechanisms of these bisphosphane Pt(II) compounds, the reactions of selected complexes against the model protein cytochrome c were investigated by ESI-MS and their adduct formation explored. A relevant reactivity with cyt c was obtained only for cis-PtP(2)Cl(2) compounds, whereas cis-PtP(2)S(2) compounds turned out to be nearly unreactive. The obtained results are interpreted and discussed in the frame of the current knowledge of anticancer platinum compounds and their structure-activity-relationships. The observation of appreciable antiproliferative effects for the relatively inert cis-PtP(2)S(2) compounds strongly suggests that these compounds will undergo specific activation within the cellular environment.     

Chemistry of trans-resveratrol with singlet oxygen: [2+2] addition, [4+2] addition, and formation of the phytoalexin moracin M

Resveratrol (1) reacts with singlet oxygen by two major pathways: A [2+2] cycloaddition forming a transient dioxetane that cleaves into the corresponding aldehydes and a [4+2] cycloaddition forming an endoperoxide that, upon heating, undergoes a rearrangement to moracin M. The rate constant by which singlet oxygen is removed by 1 (k(T)) was determined by time-resolved infrared luminescence spectroscopy to be 1.5 × 10(6) M(-1) sec(-1) in CD(3)OD, smaller than previously reported values. Chemical reaction accounts for ca. 25% of k(T).     

Optical properties of a polyethylene dispersion with a luminescent silica prepared by surface grafting of a perylene derivative

A micrometric silica modified with perylene derivative (SiO₂–TES) has been prepared by hydrolysis–condensation reactions between silica and N,N’-bis-(3-triethoxysilylpropyl)-perylene-tetracarboxyldiimide (P-TES) and utilized as filler in LLDPE films together with a compatibilizer. Spectroscopic analyses on SiO₂–TES confirmed the grafting of P-TES on silica, while its amount was determined by thermogravimetric analysis. Solid state NMR provided information about the structure of silicon atoms involved in the condensation of SiO₂ and P-TES that resulted mainly in silicon atoms grafted with bi-dentate anchorages.UV–Vis and fluorescence analyses carried out on P-TES showed the ability of the dye to generate J-type aggregates in apolar solvents. The same analyses on SiO₂–TES revealed the presence of both isolated and aggregated dye molecules grafted on silica surface, while on polymeric dispersions of SiO₂–TES, they have shown only the presence of P-TES aggregates grafted to silica.Thanks to the direct correlation between optical properties (obtained both by UV–Vis and by fluorescence analyses) and the chemical environment of composites, the luminescent silica SiO₂–TES could be used to estimate the filler dispersion extent in different microcomposite polymer materials.