Influence of Glycerol on the polymorphic Behavior of solid Triglyceride Nanoparticles stabilized with Poly(vinyl Alcohol)

Colloidal dispersions of lipids, e.g. triglycerides, are under intensive investigation as drug delivery systems. Solid triglyceride nanoparticles exist in different polymorphic modifications. The aim of this study was to investigate the effects of the addition of glycerol, which can be used for the isotonization of such dispersions, on the polymorphic behavior of poly(vinyl alcohol)-stabilized tripalmitin nanoparticles. Glycerol was added to the nanoparticle dispersions at different concentrations in the heat. The dispersions were investigated for their thermal behavior and storage stability with regard to particle size and polymorphic transitions of the triglyceride matrix, using photon correlation spectroscopy, differential scanning calorimetry and X-ray diffraction. The addition of glycerol led to a decreasing crystallization temperature of the nanoparticles and slowed down the polymorphic transition into the stable β-modification

Parameters influencing Ostwald ripening of Nanoemulsions produced by Premix Membrane Emulsification

Premix membrane emulsification is a promising method to produce colloidal lipid carrier systems, e.g. triglyceride nanoemulsions, with small particle sizes and narrow particle size distributions for intravenous administration. The stability of these systems can be affected by Ostwald ripening. The process of Ostwald ripening in emulsions of medium chain triglycerides stabilized with sucrose laurate was monitored by particle size measurements with photon correlation spectroscopy. Two different preparation methods were used and the concentration of free emulsifier measured to learn more about the influencing parameters. The concentration of free sucrose laurate turned out to be the main influencing parameter and should be about zero to minimize Ostwald ripening in the emulsions

Formulation of Cannabidiol in Lipid Carriers

Substances extracted from Cannabis varieties are of increasing interest, especially cannabidiol as a non-psychoactive drug with various pharmacological effects. Formulation of cannabidiol is, however, challenging due to its low water solubility. In this study, different types of lipid carriers were investigated as formulation options for cannabidiol to enable parenteral or oral application. The study included self-dispersing lipid formulations, nanoemulsions and liposomes. With regard to parenteral application, a higher load of cannabidiol was obtained in nanoemulsions than in liposomes. Lipid nanoemulsions are thus a very promising formulation option for parenteral formulations with a high drug load. Also in formulations intended for oral use a notably higher amount of cannabidiol could be incorporated in oil-containing self-dispersing formulations than in liposomes

Do you know this syndrome? Nail patela syndrome: a pathognomonic dermatologic finding

Hosp Barra DOr, Unidade Neurointens, Rio De Janeiro, RJ, BrazilUniv Fed Sao Paulo UNIFESP, Dept Clin Med, Escola Paulista Med, Sao Paulo, SP, BrazilHosp Barra DOr, Intens Care Dept, Rio De Janeiro, RJ, BrazilUniv Fed Sao Paulo UNIFESP, Dept Clin Med, Escola Paulista Med, Sao Paulo, SP, BrazilWeb of Scienc

The Role of Complement in HSCT-TMA : Basic Science to Clinical Practice

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a common complication occurring post-HSCT and is associated with substantial morbidity and mortality if not promptly identified and treated. Emerging evidence suggests a central role for the complement system in the pathogenesis of HSCT-TMA. The complement system has also been shown to interact with other pathways and processes including coagulation and inflammation, all of which are activated following HSCT. Three endothelial cell-damaging "hits" are required for HSCT-TMA genesis: a genetic predisposition or existing damage, an endothelial cell-damaging conditioning regimen, and additional damaging insults. Numerous risk factors for the development of HSCT-TMA have been identified (including primary diagnosis, graft type, and conditioning regimen) and validated lists of relatively simple diagnostic signs and symptoms exist, many utilizing routine clinical and laboratory assessments. Despite the relative ease with which HSCT-TMA can be screened for, it is often overlooked or masked by other common post-transplant conditions. Recent evidence that patients with HSCT-TMA may also concurrently present with these differential diagnoses only serve to further confound its identification and treatment. HSCT-TMA may be treated, or even prevented, by removing or ameliorating triggering "hits", and recent studies have also shown substantial utility of complement-targeted therapies in this patient population. Further investigation into optimal management and treatment strategies is needed. Greater awareness of TMA post-HSCT is urgently needed to improve patient outcomes; the objective of this article is to clarify current understanding, explain underlying complement biology and provide simple tools to aid the early recognition, management, and monitoring of HSCT-TMA.Peer reviewe

Structure and Non-Equilibrium Heat-Transfer of a Physisorbed Molecular Layer on Graphene

The structure of a physisorbed sub-monolayer of 1,2-bis(4-pyridyl)ethylene (bpe) on epitaxial graphene is investigated by Low-Energy Electron Diffraction and Scanning Tunneling Microscopy. Additionally, non-equilibrium heat-transfer between bpe and the surface is studied by Ultrafast Low-Energy Electron Diffraction. Bpe arranges in an oblique unit cell which is not commensurate with the substrate. Six different rotational and/or mirror domains, in which the molecular unit cell is rotated by 28{\pm}0.1{\deg} with respect to the graphene surface, are identified. The molecules are weakly physisorbed, as evidenced by the fact that they readily desorb at room temperature. At liquid nitrogen temperature, however, the layers are stable and time-resolved experiments can be performed. The temperature changes of the molecules and the surface can be measured independently through the Debye-Waller factor of their individual diffraction features. Thus, the heat flow between bpe and the surface can be monitored on a picosecond timescale. The time-resolved measurements, in combination with model simulations, show the existence of three relevant thermal barriers between the different layers. The thermal boundary resistance between the molecular layer and graphene was found to be 2{\pm}1{\cdot}10-8 K m2 W-1

Release of TGF-β3 from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal Cells

The design of implants for tissue transitions remains a major scientific challenge. This is due to gradients in characteristics that need to be restored. The rotator cuff in the shoulder, with its direct osteo-tendinous junction (enthesis), is a prime example of such a transition. Our approach towards an optimized implant for entheses is based on electrospun fiber mats of poly(ε-caprolactone) (PCL) as biodegradable scaffold material, loaded with biologically active factors. Chitosan/tripolyphosphate (CS/TPP) nanoparticles were used to load transforming growth factor-β3 (TGF-β3) with increasing loading concentrations for the regeneration of the cartilage zone within direct entheses. Release experiments were performed, and the concentration of TGF-β3 in the release medium was determined by ELISA. Chondrogenic differentiation of human mesenchymal stromal cells (MSCs) was analyzed in the presence of released TGF-β3. The amount of released TGF-β3 increased with the use of higher loading concentrations. This correlated with larger cell pellets and an increase in chondrogenic marker genes (SOX9, COL2A1, COMP). These data were further supported by an increase in the glycosaminoglycan (GAG)-to-DNA ratio of the cell pellets. The results demonstrate an increase in the total release of TGF-β3 by loading higher concentrations to the implant, which led to the desired biological effect

Formulation of Cannabidiol in Colloidal Lipid Carriers

In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to −60 °C