Liposomes loaded with daunorubicin and an emetine prodrug for improved selective cytotoxicity towards acute myeloid leukaemia cells.

The backbone of induction therapy in acute myeloid leukaemia (AML) is to use an anthracycline in combination with cytarabine. Despite recent advances in AML therapy, this treatment remains the standard, and it has been largely unchanged for decades. There are few curative options for patients unfit for this treatment.

Thermodynamic and structural properties of lipid-photosensitizer conjugates mixed with phospholipids: Impact on the formation and stability of nano-assemblies.

The photosensitizer Phenalenone (PN) was grafted with one or two lipid (C) chains to form pure nano-assemblies or mixed lipid vesicles suitable for photodynamic therapy. Mixtures of PN-C conjugates with stearoyl-oleoyl phosphatidylcholine (SOPC) form vesicles that disintegrate into bilayer sheets as the concentration of PN-C conjugates increases. We hypothesized that PN-C conjugates control the thermodynamic and structural properties of the mixtures and induce the disintegration of vesicles due to PN π-π-interactions.

PLA-PEG forming worm-like nanoparticles despite unfavorable packing parameter: Formation mechanism, thermal stability and potential for cell internalization.

Most nanoparticles produced for drug delivery purposes are spherical. However, the literature suggests that elongated particles are advantageous, notably in terms of cellular uptake. Thus, we synthesized biocompatible polylactide-b-poly(ethylene glycol) (PLA-PEG) polymers bearing carboxylate moieties, and used them to formulate worm-like nanoparticles by a simple emulsion-evaporation process.

Organization of the Interfacial Film of Nanoemulsions Stabilized by Porphyrin Derivatives.

Photodynamic therapies combining the action of a photosensitizer (PS), molecular oxygen, and light make it possible to destroy certain infectious sites and tumors. The incorporation of photosensitizers in nanocarriers allows for better control of their distribution in tissues and increases their concentration in the area that will be then illuminated. Nanoemulsions of glyceryl trioctanoate (GTO) have been designed in which pyropheophobide (Pyro-A) or its lipid conjugate (Pyro-Lipid) are both stabilizing and photostimulable agents.

Interplay between mucus mobility and alveolar macrophage targeting of surface-modified liposomes.

Alveolar macrophages play a crucial role in the initiation and resolution of the immune response in the lungs. Pro-inflammatory M1 alveolar macrophages are an interesting target for treating inflammatory and infectious pulmonary diseases. One commune targeting strategy is to use nanoparticles conjugated with hyaluronic acid, which interact with CD44 overexpressed on the membrane of those cells.

Polylactide Perspectives in Biomedicine: From Novel Synthesis to the Application Performance.

The incessant developments in the pharmaceutical and biomedical fields, particularly, customised solutions for specific diseases with targeted therapeutic treatments, require the design of multicomponent materials with multifunctional capabilities. Biodegradable polymers offer a variety of tailored physicochemical properties minimising health adverse side effects at a low price and weight, which are ideal to design matrices for hybrid materials. PLAs emerge as an ideal candidate to develop novel materials as are endowed withcombined ambivalent performance parameters.

Multifunctional PLA/Gelatin Bionanocomposites for Tailored Drug Delivery Systems.

A series of bionanocomposites composed of shark gelatin hydrogels and PLA nanoparticles featuring different nanostructures were designed to generate multifunctional drug delivery systems with tailored release rates required for personalized treatment approaches. The global conception of the systems was considered from the desired customization of the drug release while featuring the viscoelastic properties needed for their ease of storage and posterior local administration as well as their biocompatibility and cell growth capability for the successful administration at the biomolecular level. The hydrogel matrix offers the support to develop a direct thermal method to convert the typical kinetic trapped nanostructures afforded by the formulation method whilst avoiding the detrimental nanoparticle agglomeration that diminishes their therapeutic effect.

Synthesis of High Molecular Weight Stereo-Di-Block Copolymers Driven by a Co-Initiator Free Catalyst.

Stereo-diblock copolymers of high molecular weight polylactide (PLA) were synthetized by the one pot-sequential addition method assisted by a heteroscorpionate catalyst without the need of a co-initiator. The alkyl zinc organometallic heteroscorpionate derivative (Zn(Et)(κ-bpzteH)] (bpzteH = 2,2-bis(3,5-dimethylpyrazol-1-yl)-1-para-tolylethoxide) proved to assist in the mechanism of reaction following a coordination-insertion process. Kinetic studies along with the linear correlation between monomer and number average molecular weight (M) conversion, and the narrow polydispersities supported the truly living polymerization character of the initiator, whereas matrix-assisted laser desorption/Ionization-time of flight (MALDI-TOF) studies showed a very low order of transesterification.

Deciphering the Peculiar Behavior of β-Lapachone in Lipid Monolayers and Bilayers.

β-Lapachone (β-Lap) is a promising anticancer drug whose applications have been limited so far because of its poor solubility and stability. Its encapsulation in liposomes has been proposed to overcome these issues. However, surface pressure measurements show that β-Lap exhibits atypical interfacial behavior when mixed with lipids.

Stacking as a Key Property for Creating Nanoparticles with Tunable Shape: The Case of Squalenoyl-Doxorubicin.

The development of elongated nanoparticles for drug delivery is of growing interest in recent years, due to longer blood circulation and improved efficacy compared to spherical counterparts. Squalenoyl-doxorubicin (SQ-Dox) conjugate was previously shown to form elongated nanoparticles with improved therapeutic efficacy and decreased toxicity compared to free doxorubicin. By using experimental and computational techniques, we demonstrate here that the specific physical properties of SQ-Dox, which include stacking and electrostatic interactions of doxorubicin as well as hydrophobic interactions of squalene, are involved in the formation of nanoassemblies with diverse elongated structures.

Time evolution of Symmetry-forbidden Raman lines activated by photorefractivity.

Transmission Raman spectroscopy experiments were performed on iron doped congruent lithium niobate within two -in principle equivalent- configurations, namely Y(ZX)Y and Y(XZ)Y. While the former respects the Raman selection rules, the other configuration gives a time dependent spectrum that, after a transient time of several minutes, finally results in a mixture of expected and forbidden modes. This breaking of Raman selection rules is caused by the spontaneous conversion of a part of the ordinarily polarized pump beam into an extraordinarily polarized beam by photorefractive anisotropic self-scattering.

Bare and Sterically Stabilized PLGA Nanoparticles for the Stabilization of Pickering Emulsions.

Pickering emulsions were formulated using biodegradable and biocompatible poly(lactic- co-glycolic acid) (PLGA) nanoparticles (NPs) prepared without surfactants or any other polymer than PLGA. A pharmaceutical and cosmetic oil (Miglyol) was chosen as the oil phase at a ratio of 10% w/w. These emulsions were then compared with emulsions using the same oil but formulated with well-described PLGA-poly(vinyl alcohol) (PVA) NPs, i.

Dexamethasone palmitate large porous particles: A controlled release formulation for lung delivery of corticosteroids.

We have optimized a formulation of a prodrug of dexamethasone (DXM), dexamethasone palmitate (DXP) for pulmonary delivery as a dry powder. Formulations were prepared by spray drying DXP with 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Hyaluronic Acid (HA) as excipients. Large porous particles around 13 μm were produced with a tap density of 0.

Polysaccharide-coated liposomes by post-insertion of a hyaluronan-lipid conjugate.

Hyaluronan (MW: 1.5 MDa) was linked to a phospholipid (dipalmitoyl phosphatidylethanolamine, DPPE) by an amidification procedure to obtain novel macromolecules (HA-DPPE) able to coat liposomes. Liposomes made of dipalmitoyl phosphatidylcholine and cholesterol (DPPC/Chol: 95/5 molar ratio), with a mean size around 100nm, were incubated with HA-DPPE at 55°C, allowing the insertion of DPPE moieties in the liposomal bilayer and leading to hyaluronan-coated liposomes (HAsomes) as evidenced by several techniques including dynamic light scattering and differential scanning calorimetry.

Impact of lipid composition and photosensitizer hydrophobicity on the efficiency of light-triggered liposomal release.

Photo-triggerable liposomes are considered nowadays as promising drug delivery devices due to their potential to release encapsulated drugs in a spatial and temporal manner. In this work, we have investigated the photopermeation efficiency of three photosensitizers (PSs), namely verteporfin, pheophorbide a and m-THPP when incorporated into liposomes with well-defined lipid compositions (SOPC, DOPC or SLPC). By changing the nature of phospholipids and PSs, the illumination of the studied systems was shown to significantly alter their lipid bilayer properties via the formation of lipid peroxides.

Peculiar reduction of graphene oxide into graphene after diffusion in exponentially growing polyelectrolyte multilayers.

In the present work, in situ reduction of graphene oxide (GO) into graphene was preformed, after diffusion in exponentially growing polyelectrolyte multilayers, using sodium citrate as the reducing agent. First, the graphene oxide was obtained by treating a commercial grade of Expanded Graphite (EG). Based on XRD and Raman spectroscopy results, a complete exfoliation of graphene nanopellets down to one layer was achieved during the oxidation process.

Quasi-phase-matched gratings printed by all-optical poling in polymer films.

The all-optical poling technique permits polar orientation of molecules. For efficient poling of thin films the relative phases, amplitudes, and polarizations of the two interfering beams must be controlled. We present an original stable one-arm interferometer that is specific to the recording of two-color interference.

Concentration-dependent tubular secretion of acetazolamide and its inhibition by salicylic acid in the isolated perfused rat kidney.

An isolated perfused rat kidney (IPK) technique was used to study the effect of salicylic acid (SA) on the excretion of acetazolamide (AZ). Initial experiments were conducted in the absence of interactants at three nominal AZ concentrations (50, 100, and 250 micrograms/ml). Over the concentration range studied, AZ demonstrated net tubular secretion in the IPK.

Lymphopenic effect of carbamazepine in a patient with chronic lymphocytic leukemia.

Objective: To report a dramatic and reproducible suppressive effect of carbamazepine on circulating lymphocytes in an elderly woman with chronic lymphocytic leukemia.

Case Summary: An elderly woman taking phenytoin for a stroke-associated seizure disorder had lymphocyte count of 28,800 x 10(6) cells/L. Speculating an unusual lymphadenopathic effect of the phenytoin therapy, carbamazepine therapy was substituted.

Gastric retention of enteric-coated magnesium chloride tablets.

Objective: To describe a patient with gastric retention of enteric-coated magnesium chloride tablets. Potential drug and disease etiologies accounting for failure to empty this dosage form are discussed.

Design: Single case report.

Unmasking the significant enzyme-inducing effects of phenytoin on serum carbamazepine concentrations during phenytoin withdrawal.

Objective: We report on two patients who appeared to exhibit profound induction of carbamazepine metabolism during cotherapy with phenytoin. Gradual withdrawal of phenytoin confirmed this impression.

Design: Two case studies.

Elucidating the relationship between acetazolamide plasma protein binding and renal clearance using an albumin infusion.

The effect of plasma protein binding changes on drug clearance is an important concept in clinical pharmacology. In a hypoalbuminemic patient receiving acetazolamide, albumin infusion (50 g) increased acetazolamide plasma protein binding towards normal as the serum albumin concentration rose (r = 0.91, P < .