In Vivo Evaluation of the Biocompatibility of Surface Modified Hemodialysis Polysulfone Hollow Fibers in Rat

Polysulfone (Psf) hollow fiber membranes (HFMs) have been widely used in blood purification but their biocompatibility remains a concern. To enhance their biocompatibility, Psf/TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate) composite HFMs and 2-methacryloyloxyethyl phosphorylcholine (MPC) coated Psf HFMs have been prepared. They have been evaluated for in vivo biocompatibility and graft acceptance and compared with sham and commercial membranes by intra-peritoneal implantation in rats at day 7 and 21. Normal body weights, tissue formation and angiogenesis indicate acceptance of implants by the animals. Hematological observations show presence of post-surgical stress which subsides over time. Serum biochemistry results reveal normal organ function and elevated liver ALP levels at day 21. Histological studies exhibit fibroblast recruitment cells, angiogenesis and collagen deposition at the implant surface indicating new tissue formation. Immuno-histochemistry studies show non-activation of MHC molecules signifying biocompatibilty. Additionally, Psf/TPGS exhibit most favorable tissue response as compared with other HFMs making them the material of choice for HFM preparation for hemodialysis applications

Islet-Like Cell Aggregates Generated from Human Adipose Tissue Derived Stem Cells Ameliorate Experimental Diabetes in Mice

BACKGROUND: Type 1 Diabetes Mellitus is caused by auto immune destruction of insulin producing beta cells in the pancreas. Currently available treatments include transplantation of isolated islets from donor pancreas to the patient. However, this method is limited by inadequate means of immuno-suppression to prevent islet rejection and importantly, limited supply of islets for transplantation. Autologous adult stem cells are now considered for cell replacement therapy in diabetes as it has the potential to generate neo-islets which are genetically part of the treated individual. Adopting methods of islet encapsulation in immuno-isolatory devices would eliminate the need for immuno-suppressants. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we explore the potential of human adipose tissue derived adult stem cells (h-ASCs) to differentiate into functional islet like cell aggregates (ICAs). Our stage specific differentiation protocol permit the conversion of mesodermic h-ASCs to definitive endoderm (Hnf3β, TCF2 and Sox17) and to PDX1, Ngn3, NeuroD, Pax4 positive pancreatic endoderm which further matures in vitro to secrete insulin. These ICAs are shown to produce human C-peptide in a glucose dependent manner exhibiting in-vitro functionality. Transplantation of mature ICAs, packed in immuno-isolatory biocompatible capsules to STZ induced diabetic mice restored near normoglycemia within 3-4 weeks. The detection of human C-peptide, 1155±165 pM in blood serum of experimental mice demonstrate the efficacy of our differentiation approach. CONCLUSIONS: h-ASC is an ideal population of personal stem cells for cell replacement therapy, given that they are abundant, easily available and autologous in origin. Our findings present evidence that h-ASCs could be induced to differentiate into physiologically competent functional islet like cell aggregates, which may provide as a source of alternative islets for cell replacement therapy in type 1 diabetes

In vitro evaluation of surfactants with eucalyptus oil for respiratory distress syndrome

The effects of low doses of eucalyptus oil (EO) were studied on the surface properties of phospholipid suspensions as exogenous surfactants, by in vitro analysis using a pulsating bubble surfactometer and a Wilhelmy balance. Survanta, ALEC and Exosurf, commonly used surfactants in therapy of respiratory distress syndrome were used as controls for comparison. The test surfactants, in Ringer's lactate at 1%, were pulsated at 40 cpm in the surfactometer. EO caused a significant improvement of adsorption of the surfactants. In the case of the binary mixture of dipalmitoylphosphatidylcholine and phosphatidylethanolamine (2:3), EO significantly improved the adsorption, stability and minimum surface tension obtained. This combination performed better than ALEC and Exosurf and was comparable to Survanta with respect to minimum surface tension attained. The re-spreading of a surface excess film of this mixture in a Wilhelmy balance was higher than that of ALEC and Exosurf. The ultrastructure of the EO enriched surfactants using cryogenic scanning electron microscopy showed easy facturability and formation of open membranous structures, which could have been associated with the improved surface activity.© Elsevie

Concomitant Effect of Quercetin- and Magnesium-Doped Calcium Silicate on the Osteogenic and Antibacterial Activity of Scaffolds for Bone Regeneration

Quercetin is a bioflavonoid which has a broad spectrum of biological activity. Due to its lower chemical stability, it is usually encapsulated, or a metal–quercetin complex is formed to enhance its biological activity at a lower concentration. Here, our novel approach was to form a quercetin complex to magnesium-doped calcium silicate (CMS) ceramics through a coprecipitation technique so as to take advantage of quercetin’s antibacterial activity within the antibacterial and osteogenic potential of the silicate. Due to quercetin’s inherent metal-chelating ability, (Ca+Mg)/Si increased with quercetin concentration. Quercetin in magnesium-doped calcium silicate ceramic showed concentration-dependent pro-oxidant and antioxidant activity in SaOS-2 with respect to quercetin concentration. By optimizing the relative concentration, we were able to achieve 3-fold higher proliferation and 1.6-fold higher total collagen at day 14, and a 1.7-fold higher alkaline phosphatase production at day 7 with respect to polycaprolactone/polyvinylpyrrolidone (PCL/PVP) scaffold. Quercetin is effective against Gram-positive bacteria such as S. aureus. Quercetin is coupled with CMS provided similar effect with lower quercetin concentration than quercetin alone. Quercetin reduced bacterial adhesion, proliferation and biofilm formation. Therefore, quercetin-coupled magnesium-doped calcium silicate not only enhanced osteogenic potential, but also reduced bacterial adhesion and proliferation

Effect of phospholipid mixtures and surfactant formulations on rheology of polymeric gels, simulating mucus, at shear rates experienced in the tracheobronchial tree

A surface active layer consisting mainly of phospholipids lines the human conducting airways. Dysfunction of this layer could play a role in the pathogenesis of chronic obstructive airway diseases like asthma and chronic bronchitis. Replacement therapy with exogenous surfactants is being considered in such conditions. The relationship between surfactants and mucus viscosity would be important for such an application. Respiratory mucus is composed of high molecular weight glycoprotein molecules which form temporary cross-links and entanglements to form a gel-like material. The present paper studies the interaction of three therapeutic surfactants — Exosurf, ALEC and Survanta; the main phospholipids of lung surfactant (1,2-dipalmitoyl phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG)) as well as their binary mixtures (PCPE and PCPG) in a PC:(PE or PG) ratio of 2:3; on the viscosity of mucus gel simulants (MGS — a polymeric gel consisting mainly of gum tragacanth and simulating respiratory mucus). The surfactants were studied with respect to their ability to alter MGS viscosity at shear rates ranging from 0.1498 to 51.2 s−1 in a concentric cylinder viscometer at 37°C. The change in viscosity of the MGS on incubation with surfactant versus shear rate was found be non-Newtonian and to follow a power law model (coefficient of regression R2≥0.9). The shear rates experienced by a surfactant mixture, while passing through the tracheobronchial tree, were then calculated by modelling the tracheobronchial tree as cylindrical branching tubes. The equation governing the flow of a power law fluid through a cylindrical pipe was used to determine the shear experienced by a surfactant infusion as it passes through various mucus lined branches of the tracheobronchial tree. The surfactants were then compared based on their ability to alter MGS viscosity at shear rates corresponding to that of large, medium and small bronchi, as calculated by the study.© Elsevie

Self-assembled surfactant nano-structures important in drug delivery: A review

133-159Role of self assembled structures as a vehicle is significant over the years. Their applications have been found for all routes of drug delivery. These micro and nano structures are containers loaded with drugs, ideal for targeted and sustained release of the drug. Drug efficacy depends on the drug loaded into the vehicle, temperature, drug solubility, pH, release characteristics, additives and most significantly, the vehicle morphology. This in turn suggests that the same vehicle cannot be used with high efficiency for all types of drugs and locations where the drug delivery has to take place. The status of various self assembled structures and their applications in drug delivery is reviewed in this communication