Advantages of a New Low-Cost Negative Pressure Wound Therapy Using the "Turtle VAC": A Case Series.

Case: We present a clinical case and technique guide demonstrating the use and effectiveness of a novel, low-cost negative pressure wound therapy (NPWT) device to achieve soft-tissue coverage in a 34-year-old patient with failed rotational flap and Masquelet technique on infected tibial nonunion. Local debridement was executed, NPWT initiated, and treatment culminated with complete wound healing.

Conclusion: The "Turtle VAC" offers an effective low-cost alternative to commercially vacuum-assisted closure systems for post-traumatic wounds in low-resource setting of Haiti.

Contribution of Intrinsic Fluorescence to the Design of a New 3D-Printed Implant for Releasing SDABS.

Single-domain antibodies (sdAbs) offer great features such as increased stability but are hampered by a limited serum half-life. Many strategies have been developed to improve the sdAb half-life, such as protein engineering and controlled release systems (CRS). In our study, we designed a new product that combined a hydrogel with a 3D-printed implant.

The contribution of milks and formulae to micronutrient intake in 1-3 years old children in urban China: a simulation study.

Background And Objectives: A recent dietary survey in 5 big cities in China provided information on various milk options consumed by 1-3 years old children. To investigate the nutritional role of these milks (young-child formula (YCF), cow's milk, others), simulation analyses based on this survey were performed.

Methods And Study Design: We studied daily intakes of calcium, iron, zinc, vitamins A, B-1, B-2, C and E and compared these to the Chinese DRIs.

Influence of PLA-PEG nanoparticles manufacturing process on intestinal transporter PepT1 targeting and oxytocin transport.

Oral administration of peptides still remains a challenging issue. We previously pointed out the possibility to target intestinal PepT1 transporter with functionalized PLA-PEG nanoparticles (NPs) formulated by nanoprecipitation, and to improve drug-loaded intestinal permeability. Nevertheless, alternative manufacturing processes exist and the impact on the intestinal transporter targeting could be interesting to study.

Double or Simple Emulsion Process to Encapsulate Hydrophilic Oxytocin Peptide in PLA-PEG Nanoparticles.

Purpose: Oral drug delivery using NPs is a current strategy for poorly absorbed molecules. It offers significant improvement in terms of bioavailability. However, the encapsulation of proteins and peptides in polymeric NPs is a challenge.

Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir.

Targeting intestinal di- and tri-peptide transporter PepT1 with prodrugs is a successful strategy to improve oral drug bioavailability, as demonstrated with valacyclovir, a prodrug of acyclovir. The aim of this new drug delivery strategy is to over-concentrate a poorly absorbed drug on the intestinal membrane surface by targeting PepT1 with functionalized polymer nanoparticles. In the present study, poly(lactic acid)-poly(ethylene glycol)-ligand (PLA-PEG-ligand) nanoparticles were obtained by nanoprecipitation.

Optimization of magnetic retention in the gastrointestinal tract: Enhanced bioavailability of poorly permeable drug.

Oral administration of low permeable drugs remains a challenge as they do not cross biological membrane efficiently and therefore exhibit a poor bioavailability. Herein, the effect of magnetic retention on the circulation and bioavailability of magnetic beads in the gastrointestinal tract in the presence of an external magnetic field is evaluated. Retention efficiency is imaged using magnetic resonance and near infrared techniques.

Theoretical Impact of Replacing Whole Cow's Milk by Young-Child Formula on Nutrient Intakes of UK Young Children: Results of a Simulation Study.

Background: Research into the role of young-child formulae (YCF) in a child's diet is limited and there is no consensual recommendation on its use. We evaluated the theoretical nutritional impact of replacing the existing practice of consuming cow's milk by YCF.

Methods: From the UK Diet and Nutrition Survey of Infants and Young Children, whole cow's milk consumers, aged 12-18 months (n = 591) were selected for simulation scenarios.

Performance of magnetic chitosan-alginate core-shell beads for increasing the bioavailability of a low permeable drug.

This work reports the synthesis and performance of magnetic chitosan-alginate core-shell beads for oral administration of small molecules in order to increase their bioavailability. For this purpose, we designed magnetic core-shell beads suitable for oral delivery that are resistant in acidic media (stomach pH), mucoadhesive, exhibit a superparamagnetic behavior and a very high entrapment efficiency. Ex vivo experiments were performed in Ussing chambers, to emphasize the effect of magnetic accumulation.

Comparative static curing versus dynamic curing on tablet coating structures.

Curing is generally required to stabilize film coating from aqueous polymer dispersion. This post-coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the coating equipment stands for an attractive industrial application.

Comprehensive study of dynamic curing effect on tablet coating structure.

The dissolution method is still widely used to determine curing end-points to ensure long-term stability of film coatings. Nevertheless, the process of curing has not yet been fully investigated. For the first time, joint techniques were used to elucidate the mechanisms of dynamic curing over time from ethylcellulose (Aquacoat)-based coated tablets.

Novel surfactants with diglutamic acid polar head group: drug solubilization and toxicity studies.

Purpose: Novel surfactants made of diglutamic acid (DG) polar head linked to lithocholic, arachidonic, linoleic or stearic acids were designed for drug solubilization.

Methods: Surfactants 3-D conformer and packing parameter were determined by molecular modelling and self-assembling properties by pyrene fluorescence measurements. Cytotoxicity was assessed on Human Umbilical Vein Endothelial Cells (HUVEC) and haemolyitic activity on rat red blood cells.

Drug solubilization and in vitro toxicity evaluation of lipoamino acid surfactants.

To improve solubilization of a water insoluble anticancer drug, novel surfactants were synthesized. All surfactants derived from lysine, with a so-called nitrilo triacetic acid (NTA) polar head, and differed from the length and saturation degree of their hydrophobic moieties: C19:0-NTA, C20:4-NTA, C25:0-NTA and C25:4-NTA. Self-assembling properties and critical micellar concentration (CMC) values were determined using pyrene fluorescence and cytotoxicity using MTT and LDH assays on endothelial cells.

Physicochemical characterization and toxicity evaluation of steroid-based surfactants designed for solubilization of poorly soluble drugs.

To overcome poor water-solubility of new drug candidates, four innovative surfactants based on naturally-occuring hydrophilic and hydrophobic moities were designed and synthesized: cholesteryl-glutamic acid, cholesteryl-poly[N-2-hydroxyethyl-l-glutamine] (PHEG), ursodeoxycholanyl-PHEG (UDCA-PHEG) and ursodeoxycholanyl-poly-l-glutamic acid (UDCA-PGA). Their self-assembling capacity was evaluated using pyrene fluorescence measurements which allow to determine their critical aggregation concentration (CAC). Size measurements were carried out using dynamic light scattering (DLS).

Real-time predictions of drug release and end point detection of a coating operation by in-line near infrared measurements.

The aim of this work was to carry out real-time near infrared (NIR) predictions of drug release from sustained release coated tablets and to determine end point of coating operation. In-line measurements were ensured by implementation of a NIR probe inside a pan coater. Tablets were coated using a functional aqueous dispersion of ethylcellulose blended with PVA-PEG graft copolymer to obtain a controlled drug release dosage form over 16h.

Development of a Process Analytical Technology (PAT) for in-line monitoring of film thickness and mass of coating materials during a pan coating operation.

The aim of this study was to perform in-line Near Infrared (NIR) measurements inside a pan coater to monitor a coating operation in real-time, by predicting the increases in mass of coating materials and coating thickness. A polymer combination of ethylcellulose/poly(vinyl-alcohol)-poly(ethylene-glycol) graft copolymer was used as functional aqueous coating. Coated tablets were sampled at regular intervals during the coating operation, then subjected to either simple and fast weighing (n=50) or accurate and non-destructive Terahertz Pulsed Imaging (TPI) measurements (n=3).

Biodistribution and anticancer activity of a new Vinca alkaloid encapsulated into long-circulating liposomes.

S12363 is a potent therapeutic agent with a strong in vitro activity against a variety of tumor types but also a high in vivo toxicity. Loading of this drug into long-circulating liposomes is expected to enhance its therapeutic index. Pharmacokinetics of liposomal S12363 showed that circulating S12363 was entrapped into liposomes until 24 hours after intravenous injection in mice.

Supramolecular organization of S12363-liposomes prepared with two different remote loading processes.

The S12363 anticancer drug was encapsulated into liposomes in an attempt to increase its therapeutic index. Loading of S12363 was achieved using two different processes based on the formation of either a pH gradient or an ammonium gradient between the acidic inner liposomal compartment and the basic outer phase. High encapsulation yields (>90%) were obtained using both processes for sphingomyelin/cholesterol/cholesterol-PEG vesicles.

[Oral bioavailability and drug/carrier particulate systems].

The oral route remains the preferred route of administration to ensure patient satisfaction and compliance. However, new chemical entities may exhibit low bioavailability after oral administration because of poor stability within the gastrointestinal tract, poor solubility in gastrointestinal fluids, low mucosal permeability, and/or extensive first-pass metabolism. Consequently, these new drug substances cannot be further developed using conventional oral formulations.

Consequences of ions and pH on the supramolecular organization of sphingomyelin and sphingomyelin/cholesterol bilayers.

For drug delivery purpose the anticancer drug S12363 was loaded into ESM/Chol-liposomes using either a pH or an ammonium gradient. Association between the drug and the liposome depends markedly on the liposome membrane structure. Thus, ESM and ESM/Chol bilayer organization had been characterized by coupled DSC and XRDT as a function of both cholesterol concentration and aqueous medium composition.

Drug/lactose co-micronization by jet milling to improve aerosolization properties of a powder for inhalation.

The aim of this work was to formulate a powder for inhalation with fusafungine, a drug substance initially highly cohesive. The classical approach based on micronization by jet milling to prepare respirable drug particles and then blending with a carrier was first applied. A fractional factorial experimental design was implemented to screen six formulation parameters.

Intraseptal implantation of NGF-releasing microspheres promote the survival of axotomized cholinergic neurons.

Neurotrophic factors therapy requires their precise delivery to the targeted neuronal population. For this purpose, a wide range of strategies have been developed, and among them the stereotaxic implantation of biodegradable microparticles. To assess the in vivo activity of NGF-releasing PLGA microspheres, unloaded and NGF-loaded microparticles were implanted in the rat brain, near the septal cholinergic neurons, axotomized by an unilateral transection of the fornix-fimbria.

Intracerebral implantation of NGF-releasing biodegradable microspheres protects striatum against excitotoxic damage.

Intrastriatal implantation of genetically modified cells synthesizing nerve growth factor (NGF) constitutes one way to obtain a long-term supply of this neurotrophic factor and a neuronal protection against an excitotoxic lesion. We have investigated if NGF-loaded poly(d,l-lactide-co-glycolide) microspheres could represent an alternative to cell transplantations. These microspheres can be implanted stereotaxically and locally release the protein in a controlled and sustained way.

High-resolution multiwavelength surface plasmon resonance spectroscopy for probing conformational and electronic changes in redox proteins.

To date, surface plasmon resonance (SPR) spectroscopy identifies molecules via specific bindings with their ligands immobilized on a surface. We demonstrate here that a high-resolution multiwavelength SPR technique can measure the electronic states of the molecules and thus allow direct identification of the molecules. Using this new capability, we have studied the electronic and conformational differences between the oxidized and reduced states of cytochrome c immobilized on a modified gold electrode.

Why does PEG 400 co-encapsulation improve NGF stability and release from PLGA biodegradable microspheres?

Purpose: The aim of this work was to understand the mechanism by which co-encapsulated PEG 400 improved the stability of NGF and allowed a continuous release from PLGA 37.5/25 microspheres.

Methods: Microparticles were prepared according to the double emulsion method.