Supercritical phase inversion of starch-poly(e-caprolactone) for tissue engineering applications

In this work, a starch-based polymer, namely a blend of starch-poly(ε-caprolactone) was processed by supercritical assisted phase inversion process. This processing technique has been proposed for the development of 3D structures with potential applications in tissue engineering applications, as scaffolds. The use of carbon dioxide as non-solvent in the phase inversion process leads to the formation of a porous and interconnected structure, dry and free of any residual solvent. Different processing conditions such as pressure (from 80 up to 150 bar) and temperature (45 and 55°C) were studied and the effect on the morphological features of the scaffolds was evaluated by scanning electron microscopy and micro-computed tomography. The mechanical properties of the SPCL scaffolds prepared were also studied. Additionally, in this work, the in vitro biological performance of the scaffolds was studied. Cell adhesion and morphology, viability and proliferation was assessed and the results suggest that the materials prepared are allow cell attachment and promote cell proliferation having thus potential to be used in some for biomedical applications.Ana Rita C. Duarte is grateful for financial support from Fundacao para a Ciencia e Tecnologia through the grant SFRH/BPD/34994/2007

Operative parameters optimization production of liposomes for the encapsulation of hydrophilic compounds using a new supercritical process

Liposomes are spherical vesicles formed by a inner aqueous core and a double lipidic layer around it. Conventional techniques for the production of liposomes are characterized by several drawbacks, like the production of micrometric vesicles, a difficult control of the Particle Size Distribution (PSD) and low encapsulation efficiencies (EE) of hydrophilic compounds. Many supercritical semi-continuous techniques were proposed in literature. They are successful in the intent of producing liposomes of smaller diameter, but the EE of hydrophilic compounds and the reproducibility are still a challenge. For this reason, it was recently proposed a new supercritical process whose aim is to invert the steps of production of liposomes, by first creating water droplets and then to fast surround them by phospholipids. We discovered that the high diffusion coefficient of phospholipids in supercritical carbon dioxide allows a fast coverage of water droplets preserving the drug content into the liposome core. In this work, hydrophilic compounds were encapsulated in the vesicles produced using SuperLip, such as Fluorescein, Bovine Serum Albumin (BSA) and Ampicillin, obtaining monodispersed spherical vesicles with a mean size from 100 to 300 nm. Operative parameters like water flow rate and lipid to water mass ratio were optimized. The EEs were evaluated with UV-Vis spectroscopy according to methods reported in literature, and obtaining high values up to 99 % for the three investigated compounds

3-D loaded scaffolds obtained by supercritical CO2 assisted process

In this work, a supercritical CO2 (SC-CO2) drying process for the formation of 3-D PVDF-HFP loaded scaffolds was tested. Experiments at pressures ranging between 150 and 250 bar and at temperatures ranging between 35 and 55?C were performed. The PVDF-HFP- acetone-ethanol solution at 15% w/w polymer was selected as the base case. The drug (amoxicillin) concentration was varied from 20 to 30% w/w with respect to PVDF-HFP. SC- CO2 drying process was confirmed to be a valid alternative to generate loaded structures; indeed, scaffolds characterized by nanometric networks (with mean pore diameter of about 300 nm) with a homogeneous drug distribution were obtained. Drug controlled release experiments were also performed and a quasi-zero order release kinetic was observed

Production, characterization and testing of antibacterial PVA membranes loaded with HA-Ag3PO4 nanoparticles, produced by SC-CO2 phase inversion

BACKGROUND: Silver-loaded hydroxyapatite nanoparticles were incorporated into poly(vinyl alcohol) (PVA) membranes obtained by supercritical CO2 (SC-CO2) assisted phase inversion. Ag3PO4 crystals of 2.2 ± 0.6 nm were dispersed in synthesized needle-like hydroxyapatite nanoparticles (20 × 65 nm) and were uniformly deposited on the internal surfaces of the PVA membranes. Operative conditions to produce membranes by SC-CO2, PVA concentration and the effect on membrane porosity and morphology were studied. RESULTS: Solutions at 20% w/w PVA produced membranes with cellular morphology and nanoporous walls, whereas 30% and 50% w/w solutions produced nanostructured membranes. Silver ions were released from PVA membranes mainly by diffusion according to the Peppas–Sahlin model. Membranes obtained at 20% w/w PVA showed a significant E. coli inhibition at an Ag concentration of 9 ppm, reaching the minimal inhibitory concentration (MIC) and improving the bactericidal activity of the nanoparticles. CONCLUSION: A concentration of Ag3PO4 crystals of about 22 ppm was calculated as being capable of completely destroying these bacteria, reaching the minimum bactericidal concentration (MBC)

Liposomes for Intra-Articular Analgesic Drug Delivery in Orthopedics: State-of-Art and Future Perspectives. Insights from a Systematic Mini-Review of the Literature.

Background and objectives: Liposomal structures are artificial vesicles composed of one or several lamellae of phospholipids which surround an inner aqueous core. Given the amphoteric nature of phospholipids, liposomes are promising systems for drug delivery. The present review provides an updated synthesis of the main techniques for the production of liposomes for orthopedic applications, focusing on the drawbacks of the conventional methods and on the advantages of high pressure techniques. Materials and Methods: Articles published in any language were systematically retrieved from two major electronic scholarly databases (PubMed/MEDLINE and Scopus) up to March 2020. Nine articles were retained based on the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. Results: Liposome vesicles decrease the rate of inflammatory reactions after local injections, and significantly enhance the clinical effectiveness of anti-inflammatory agents providing controlled drug release, reducing toxic side effects. Conclusions: This review presents an update on the improvement in musculoskeletal ailments using liposome treatment

Liposomes for intra-articular analgesic drug delivery in orthopedics: State-of-art and future perspectives. Insights from a systematic mini-review of the literature

Background and objectives: Liposomal structures are artificial vesicles composed of one or several lamellae of phospholipids which surround an inner aqueous core. Given the amphoteric nature of phospholipids, liposomes are promising systems for drug delivery. The present review provides an updated synthesis of the main techniques for the production of liposomes for orthopedic applications, focusing on the drawbacks of the conventional methods and on the advantages of high pressure techniques. Materials and Methods: Articles published in any language were systematically retrieved from two major electronic scholarly databases (PubMed/MEDLINE and Scopus) up to March 2020. Nine articles were retained based on the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines. Results: Liposome vesicles decrease the rate of inflammatory reactions after local injections, and significantly enhance the clinical effectiveness of anti-inflammatory agents providing controlled drug release, reducing toxic side effects. Conclusions: This review presents an update on the improvement in musculoskeletal ailments using liposome treatment

Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids

Supercritical or near-critical fluid processes for generating microparticles have enjoyed considerable attention in the past decade or so, with good success for substances soluble in supercritical fluids or organic solvents. In this review, we survey their application to the production of protein particles. A recently developed process known as CO2-assisted nebulization with a Bubble Dryer® (CAN-BD) has been demonstrated to have broad applicability to small-molecule as well as macromolecule substances (including therapeutic proteins). The principles of CAN-BD are discussed as well as the stabilization, micronization and drying of a wide variety of materials. More detailed case studies are presented for three proteins, two of which are of therapeutic interest: anti-CD4 antibody (rheumatoid arthritis), α1-antitrypsin (cystic fibrosis and emphysema), and trypsinogen (a model enzyme). Dry powders were formed in which stability and activity are maintained and which are fine enough to be inhaled and reach the deep lung. Enhancement of apparent activity after CAN-BD processing was also observed in some formulation and processing conditions

Stable amorphous georgeite as a precursor to a high-activity catalyst .

Copper and zinc form an important group of hydroxycarbonate minerals that include zincian malachite, aurichalcite, rosasite and the exceptionally rare and unstable—and hence little known and largely ignored1—georgeite. The first three of these minerals are widely used as catalyst precursors2, 3, 4 for the industrially important methanol-synthesis and low-temperature water–gas shift (LTS) reactions5, 6, 7, with the choice of precursor phase strongly influencing the activity of the final catalyst. The preferred phase2, 3, 8, 9, 10 is usually zincian malachite. This is prepared by a co-precipitation method that involves the transient formation of georgeite11; with few exceptions12 it uses sodium carbonate as the carbonate source, but this also introduces sodium ions—a potential catalyst poison. Here we show that supercritical antisolvent (SAS) precipitation using carbon dioxide (refs 13, 14), a process that exploits the high diffusion rates and solvation power of supercritical carbon dioxide to rapidly expand and supersaturate solutions, can be used to prepare copper/zinc hydroxycarbonate precursors with low sodium content. These include stable georgeite, which we find to be a precursor to highly active methanol-synthesis and superior LTS catalysts. Our findings highlight the value of advanced synthesis methods in accessing unusual mineral phases, and show that there is room for exploring improvements to established industrial catalysts