Acid leaching technology for post-consumer gypsum purification.

Background: Contaminants and water-soluble salts present in mechanically recycled gypsum from refurbishment and demolition (post-consumer) plasterboard waste limit its use as a secondary raw material in plasterboard manufacturing. This research addresses this limitation, developing a novel acid leaching purification technology combined with an improved mechanical pre-treatment for post-consumer gypsum valorization. Methods: Laboratory-scale acid leaching purification was performed with a borosilicate beaker, hot plate, and overhead stirrer. Stuccos were produced after calcination of gypsum at 150 °C for 3 hours. Samples were characterized through X-ray fluorescence, X-ray diffraction, thermal gravimetric analysis, scanning electron microscopy and particle size analysis. Results: Acid leaching at 90 °C for 1 h using a 5 wt% sulfuric acid solution was revealed to be the optimum purification conditions. Stuccos produced from purified gypsum under optimum conditions had similar initial setting times to that of a commercial stucco but with higher water demand, which could be reduced by optimizing the calcination conditions. A magnesium-rich gypsum was precipitated from the wastewater. Conclusions: Purified post-consumer gypsum with > 96 wt% chemical purity and calcium sulfate dihydrate content was produced. The research recommends acid neutralization prior filtration, use of gypsum particles < 2 mm in size, and stirring speed of 50 rpm to reduce the economic and environmental impacts of the acid leaching purification process at industrial scale. The magnesium-rich gypsum could potentially be marketed as soil fertilizer.

Plasterboard is a construction material constituted by a gypsum core sandwiched between two paper liners. Plasterboard waste generated in refurbishment and demolition projects, which is known as post-consumer plasterboard waste, contains contaminants such as mortar, plastics, foil and wood, and impurities originating from additives introduced during plasterboard manufacturing and from plasterboard finishings, such as paint and wallpaper. These contaminants and impurities cannot be removed with current mechanical treatments used in plasterboard recycling plants, and post-consumer plasterboard waste is disposed of in landfills. A novel acid leaching purification process was developed here and combined with a modified mechanical treatment that produces high purity recycled gypsum from post-consumer plasterboard waste that fulfils the requirements for plasterboard manufacturing. This new plasterboard recycling technology will prevent plasterboard waste landfilling and increase the recycled content in new plasterboards. As a result, mineral gypsum use in new plasterboards will be reduced, which will lower the environmental impact associated to mineral gypsum extraction and transportation.

Etoposide and olaparib polymer-coated nanoparticles within a bioadhesive sprayable hydrogel for post-surgical localised delivery to brain tumours.

Glioblastoma is a malignant brain tumour with a median survival of 14.6 months from diagnosis. Despite maximal surgical resection and concurrent chemoradiotherapy, reoccurrence is inevitable. To try combating the disease at a stage of low residual tumour burden immediately post-surgery, we propose a localised drug delivery system comprising of a spray device, bioadhesive hydrogel (pectin) and drug nanocrystals coated with polylactic acid-polyethylene glycol (NCPPs), to be administered directly into brain parenchyma adjacent to the surgical cavity. We have repurposed pectin for use within the brain, showing in vitro and in vivo biocompatibility, bio-adhesion to mammalian brain and gelling at physiological brain calcium concentrations. Etoposide and olaparib NCPPs with high drug loading have shown in vitro stability and drug release over 120 h. Pluronic F127 stabilised NCPPs to ensure successful spraying, as determined by dynamic light scattering and transmission electron microscopy. Successful delivery of Cy5-labelled NCPPs was demonstrated in a large ex vivo mammalian brain, with NCPP present in the tissue surrounding the resection cavity. Our data collectively demonstrates the pre-clinical development of a novel localised delivery device based on a sprayable hydrogel containing therapeutic NCPPs, amenable for translation to intracranial surgical resection models for the treatment of malignant brain tumours.

Ornithine-derived oligomers and dendrimers for in vitro delivery of DNA and ex vivo transfection of skin cells via saRNA.

Gene therapies are undergoing a renaissance, primarily due to their potential for applications in vaccination for infectious diseases and cancers. Although the biology of these technologies is rapidly evolving, delivery strategies need to be improved to overcome the poor pharmacokinetics and cellular transport of nucleic acids whilst maintaining patient safety. In this work, we describe the divergent synthesis of biodegradable cationic dendrimers based on the amino acid ornithine as non-viral gene delivery vectors and evaluate their potential as delivery vectors for DNA and RNA. The dendrimers effectively complexed model nucleic acids at lower N/P ratios than polyethyleneimine and outperformed it in DNA transfection experiments with ratios above 5. Remarkably, all dendrimer polyplexes at N/P = 2 achieved up to 7-fold higher protein content over an optimized PEI formulation when used for transfections with self-amplifying RNA (saRNA). Finally, transfection studies utilizing human skin explants revealed an increase of cells producing protein from 2% with RNA alone to 12% with dendrimer polyplexes, attributed to expression enrichment predominantly in epithelial cells, fibroblasts and leukocytes, with minor enrichment in NK cells, T cells, monocytes, and B cells. Overall, this study indicates the clear potential of ornithine dendrimers as safe and effective delivery vectors for both DNA and RNA therapeutics.

Poly (Glycerol Adipate): From a Functionalized Nanocarrier to a Polymeric-Prodrug Matrix to Create Amorphous Solid Dispersions.

Amorphous solid dispersions are a promising strategy to overcome poor solubility and stability limitations, reducing the crystallinity of the drug through incorporation within a polymer matrix. However, to achieve an effective amorphous solid dispersion, the polymer and drug must be compatible, otherwise the drug can undergo recrystallization. In this work, we investigated the potential of the enzymatically synthesized poly(glycerol-adipate), as a pharmaceutical tool for producing a nanoamorphous formulation. A polymeric prodrug of poly(glycerol-adipate) was synthesized by coupling mefenamic acid as drug. The amorphicity of the polymeric prodrug was assessed combining differential scanning calorimetry and polarized optical microscopy. The prodrug was then formulated into nanoparticles and studied for stability and drug release in the presence of lipase. To realize the goal of combination drug therapies for overcoming drug resistance and improving treatment outcomes, the prodrug was screened as a solubility enhancer for a series of fenamic drugs and compared with commercially available polymers commonly used in solid dispersions. Screening was carried out by developing a high-throughput miniaturized screening assay using a 2D printer to dispense the polymer and drug combinations. Finally, the collected data showed that drug conjugation could improve drug-polymer compatibility, in addition to facilitating the release of drugs by 2 different mechanisms.

Rapid formulation of redox-responsive oligo-ß-aminoester polyplexes with siRNA via jet printing.

Here we describe a rapid inkjet formulation method for screening newly-synthesised cationic materials for siRNA delivery into cancer cells. Reduction responsive oligo-ß-aminoesters were prepared and evaluated for their ability to condense siRNA into polyplexes through a fast inkjet printing method. A direct relationship between the oligomer structures and charge densities, and the final cell response in terms of uptake rate and transfection efficacy, was found. The oligo-ß-aminoesters were well-tolerated by the cancer cells, compared to conventional cationic polymers so far employed in gene delivery, and were as active in silencing of a representative luciferase gene.

PPh3-derivatives of [Pt3n(CO)6n]2- (n = 2-6) Chini's clusters: syntheses, structures, and 31P NMR studies.

The reaction of the [Pt3n(CO)6n](2-) (n = 2-6) Chini's clusters with increasing amounts of PPh3 has been investigated in detail by combined FT-IR, (31)P{(1)H} NMR, and electrospray ionization-mass spectrometry (ESI-MS) studies, showing that up to three CO ligands are gradually substituted by PPh3, resulting in isonuclear phosphine-substituted anionic clusters of general formula [Pt3n(CO)(6n-x)(PPh3)(x)](2-) (n = 2-6; x = 1-3). Further addition of PPh3 results in the elimination of the neutral Pt3(CO)3(PPh3)3 species and formation of lower nuclearity anionic clusters. [Pt12(CO)22(PPh3)2](2-) and [Pt9(CO)16(PPh3)2](2-) have been structurally characterized, and they maintain the trigonal prismatic structures of the parent homoleptic clusters, with the two PPh3 ligands bonded to different external Pt3-triangles in relative cis-position. Conversely, the crystal structure of [Pt6(CO)10(PPh3)2](2-) shows that its metal cage is transformed from trigonal prismatic to trigonal antiprismatic after CO/PPh3 exchange.

Self-assembly of [Pt(3n)(CO)(6n)]2- (n = 4-8) carbonyl clusters: from molecules to conducting molecular metal wires.

A comprehensive study discussing the different parameters that influence the self-assembly of [Pt(3n)(CO)(6n)](2-) (n = 4-8) clusters with miscellaneous mono- and dications into 0-D, 1-D, 2-D, and 3-D materials is herein reported. As an unexpected bonus, the use of Ru(II) dications allowed the first structural characterization of the previously unknown [Pt(21)(CO)(42)](2-) dianion. 0-D structures, which contain isolated ions, are electrical insulators in solid form. Conversely, as soon as infinite chains of clusters are formed, the electrical resistivity, measured in pressed pellets, decreases to 10(5)-10(6), 10(4), and 10(2) ohms cm for discontinuous, semicontinuous, and continuous chains, respectively. Therefore, the resemblance of these materials to molecular metal wires is not only morphological but also functional. Preliminary results of possible self-assembly phenomena in a solution of [Pt(15)(CO)(30)](2-) and [Pt(18)(CO)(36)](2-) according to dynamic light scattering experiments are also reported.