The Use of a Three-Fluid Atomising Nozzle in the Production of Spray-Dried Theophylline/Salbutamol Sulphate Powders Intended for Pulmonary Delivery.

The aim of this study was to investigate the use of a three-fluid atomising nozzle in a lab-scale spray dryer for the production of dry powders intended for pulmonary delivery. Powders were composed of salbutamol sulphate and theophylline in different weight ratios. The three-fluid nozzle technology enabled powders containing a high theophylline content to be obtained, overcoming the problems associated with its relatively low solubility, by pumping two separate feed solutions (containing the two different active pharmaceutical ingredients (APIs)) into the spray dryer via two separate nozzle channels at different feed rates.

The use of hydrophobic amino acids in protecting spray dried trehalose formulations against moisture-induced changes.

Trehalose is commonly used as a protein stabilizer in spray dried protein formulations delivered via the pulmonary route. Spray dried trehalose formulations are highly hygroscopic, which makes them prone to deliquescence and recrystallization when exposed to moisture, leading to impairment in aerosolization performance. The main aim of this study was to investigate and compare the effect of hydrophobic amino acids (i.

A Design of Experiment (DoE) approach to optimise spray drying process conditions for the production of trehalose/leucine formulations with application in pulmonary delivery.

The present study evaluates the effect of L-leucine concentration and operating parameters of a laboratory spray dryer on characteristics of trehalose dry powders, with the goal of optimizing production of these powders for inhaled drug delivery. Trehalose/L-leucine mixtures were spray dried from aqueous solution using a laboratory spray dryer. A factorial design of experiment (DoE) was undertaken and process parameters adjusted were: inlet temperature, gas flow rate, feed solution flow rate (pump setting), aspiration setting and L-leucine concentration.

The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential.

Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1), which is the master regulator in the cellular adaptive response to hypoxia.

Thixotropic Peptide-Based Physical Hydrogels Applied to Three-Dimensional Cell Culture.

Pseudopeptides containing the d-Oxd or the d-pGlu [Oxd = (4,5)-4-methyl-5-carboxyl-oxazolidin-2-one, pGlu = pyroglutamic acid] moiety and selected amino acids were used as low-molecular-weight gelators to prepare strong and thixotropic hydrogels at physiological pH. The addition of calcium chloride to the gelator solutions induces the formation of insoluble salts that get organized in fibers at a pH close to the physiological one. Physical characterization of hydrogels was carried out by morphologic evaluation and rheological measurements and demonstrated that the analyzed hydrogels are thixotropic, as they have the capability to recover their gel-like behavior.

The tumor microenvironment promotes cancer progression and cell migration.

The tumor microenvironment contributes to cancer progression, in part through interactions between tumor and normal stromal cells. This study analyzed morphological and molecular changes induced in co-cultured human fibroblasts (HFs) and the MG-63 osteosarcoma cell line. Co-cultured cell monolayers were morphologically analyzed using high resolution scanning electron microscopy (HR-SEM), and trans-well assays were performed to assess cell migration and invasion.

Calcium/Cobalt Alginate Beads as Functional Scaffolds for Cartilage Tissue Engineering.

Articular cartilage is a highly organized tissue with complex biomechanical properties. However, injuries to the cartilage usually lead to numerous health concerns and often culminate in disabling symptoms, due to the poor intrinsic capacity of this tissue for self-healing. Although various approaches are proposed for the regeneration of cartilage, its repair still represents an enormous challenge for orthopedic surgeons.

In vitro osteogenic and odontogenic differentiation of human dental pulp stem cells seeded on carboxymethyl cellulose-hydroxyapatite hybrid hydrogel.

Stem cells from human dental pulp have been considered as an alternative source of adult stem cells in tissue engineering because of their potential to differentiate into multiple cell lineages. Recently, polysaccharide based hydrogels have become especially attractive as matrices for the repair and regeneration of a wide variety of tissues and organs. The incorporation of inorganic minerals as hydroxyapatite nanoparticles can modulate the performance of the scaffolds with potential applications in tissue engineering.

HEMA but not TEGDMA induces autophagy in human gingival fibroblasts.

Polymerized resin-based materials are successfully used in restorative dentistry. Despite their growing popularity, one drawback is the release of monomers from the polymerized matrix due to an incomplete polymerization or degradation processes. Released monomers are responsible for several adverse effects in the surrounding biological tissues, inducing high levels of oxidative stress.

Stem cell origin differently affects bone tissue engineering strategies.

Bone tissue engineering approaches are encouraging for the improvement of conventional bone grafting technique drawbacks. Thanks to their self-renewal and multi-lineage differentiation ability, stem cells are one of the major actors in tissue engineering approaches, and among these adult mesenchymal stem cells (MSCs) hold a great promise for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs) are the first- identified and well-recognized stem cell population used in bone tissue engineering.

Changes in the gene expression of co-cultured human fibroblast cells and osteosarcoma cells: the role of microenvironment.

Background: The progression of malignant tumors does not depend exclusively on the autonomous properties of cancer cells; it is also influenced by tumor stroma reactivity and is under strict microenvironmental control. By themselves, stromal cells are not malignant, and they maintain normal tissue structure and function. However, through intercellular interactions or by paracrine secretions from cancer cells, normal stromal cells acquire abnormal phenotypes that sustain cancer cell growth and tumor progression.

Ultrastructural changes in human gingival fibroblasts after exposure to 2-hydroxy-ethyl methacrylate.

Polymerized resin-based materials are successfully utilized in medical applications. One draw- back is the release of monomers from the matrix due to an incomplete polymerization or degradation processes. Released monomers can diffuse in the systemic circulation and induceadverse effects to biological tissues.

Preparation and validation of low cost microfluidic chips using a shrinking approach.

The present paper describes the production of microfluidic chips using an approach based on shrinkable biocompatible polymers (i.e. agarose) for the production of size controlled microfluidic channels.

Chondrogenic differentiation of human adipose mesenchimal stem cells: influence of a biomimetic gelatin genipin crosslinked porous scaffold.

Human adipose derived stem cells have shown chondrogenic differentiation potential in cartilage tissue engineering in combination with biomimetic materials. In this study, the chondrogenic potential of a porous gelatin based scaffold genipin (GNP) crosslinked was investigated in human mesenchymal stem cells obtained from adipose tissue. Cells were cultured up to 4 weeks on the scaffold and on monolayer, MTT assay was performed to evaluate cell viability, light, and transmission electron microscopy were carried out to demonstrate cell proliferation, scaffold adhesion, and cell colonization inside the porous architecture of the biomaterial.

Anti-tumor activity of fenretinide complexed with human serum albumin in lung cancer xenograft mouse model.

Sufficient knowledge regarding cellular and molecular basis of lung cancer progression and metastasis would help in the development of novel and effective strategies for the treatment of lung cancer. 4HPR is a synthetic retinoid with potential anti-tumor activity but is still limited because of its poor bioavailability. The use of albumin as a complexing agent for a hydrophobic drug is expected to improve the water solubility and consequently their bioavailability.

Simulating tumor microenvironment: changes in protein expression in an in vitro co-culture system.

Background: The role of the microenvironment during the initiation and progression of carcinogenesis is thought to be of critical importance, both for the enhanced understanding of fundamental cancer biology as well as for improving molecular diagnostics and therapeutics. The aim of this study was to establish an in vitro model based on a co-culture of healthy human fibroblasts (HFs) and human osteosarcoma cells (MG-63s) to simulate the microenvironment including tumor and healthy cells.

Methods: The HFs and MG-63s were in vitro co-cultured for a period of time ranging from 24 h to 7 days.

Novel PLA microspheres with hydrophilic and bioadhesive surfaces for the controlled delivery of fenretinide.

Novel polylactide (PLA) microspheres endowed with hydrophilic and bioadhesive surfaces as injectable formulations for the controlled release of fenretinide were prepared, using a novel technique based on the co-precipitation of PLA with gelatin, at the interface of a liquid dispersion formed by the addition of N-methylpyrrolidone containing PLA and dextrin (DX), towards an aqueous solution of gelatin (G). The resulting PLA-G-DX microspheres were compared with others prepared by the same technique using polylactide-co-glycolide (PLGA), with or without DX, and with or without phosphatidylcholine. Of the different systems, the PLA-G-DX microspheres had the best morphological, dimensional and functional characteristics.

Gelatin crosslinked with dehydroascorbic acid as a novel scaffold for tissue regeneration with simultaneous antitumor activity.

A porous scaffold was developed to support normal tissue regeneration in the presence of residual tumor disease. It was prepared by gelatin crosslinked with dehydroascorbic acid (DHA). A physicochemical characterization of the scaffold was carried out.