Véronique Rosilio

pH-Sensitive liposomes as a carrier for oligonucleotides: a physico-chemical study of the interaction between DOPE and a 15-mer oligonucleotide in excess water

The cytoplasmic delivery of drugs encapsulated into pH-sensitive liposomes is under the control of a lamellar-to-hexagonal transition. In a previous study, under anhydrous conditions, oligonucleotides (ODN) encapsulated in pH-sensitive liposomes composed of dioleoylphosphatidylethanolamine (DOPE)/oleic acid (OA)/cholesterol (CHOL) were shown to modify the phase behaviour of DOPE. In the present study, the lipid/ODN interactions were evaluated in fully hydrated samples by surface tension measurements, differential scanning calorimetry, X-ray diffraction and turbidimetry. Concerning the lipids, it was shown that OA provoked a disorganisation of DOPE lamellar phases and led to the complete disappearance of hexagonal transition along with heating. The addition of CHOL further decreased the lipid packing in the bilayers. Concerning ODN, these molecules provoked an increase in the surface pressure of a DOPE/OA/CHOL monolayer, indicating the existence of molecular interactions with the lipids. At a supramolecular level, ODN induced a more ordered organisation of DOPE molecules in the lamellar and hexagonal phases, and completely abolished the disorganisational effect of OA and CHOL.

Cholesteryl-pullulan and cholesteryl-amylopectin interactions with egg phosphatidylcholine monolayers

Abstract The extent of adsorption of cholesteryl-pullulan and cholesteryl-amylopectin at air-water interface was assessed from the surface pressure measurements at constant area. It was found that areas per adsorbed cholesterol derivative of pullulan and amylopectin are 0.40 and 0.19 nm2, respectively. These small areas indicate that sugar moieties of both polysaccharide derivatives are completely immersed in the aqueous phase. The surface potential data strongly suggest that the cholesteryl moieties of adsorbed cholesteryl derivative of pullulan are stretched toward the air phase, but lay flat, exposing lateral CH3 groups to the interface, in the case of a cholesteryl derivative of amylopectin. Surface pressure and surface potential isotherms of egg-phosphatidylcholine monolayers were shown to be greatly modified in the presence of cholesterol-substituted polysaccharides in the aqueous subphase. The results reveal the ability of both polysaccharide derivatives to penetrate the lipid monolayer. However, this effect is superior for cholesteryl-amylopectin, which interacts strongly with the lipid even at very high surface coverages. cholesteryl-amylopectin also compensates lipid surface potential to a higher extent than cholesteryl-pullulan. This would explain why liposomes coated with cholesteryl-amylopectin exhibit lower stability relative to those coated with a cholesterol derivative of pullulan.

Specific interaction of lectins with liposomes and monolayers bearing neoglycolipids

The interaction of three lectins (wheat germ, Ulex europaeus I, and Lotus tetragonolobus agglutinins: WGA, UEA-I and LTA) with either N-acetyl-D-glucosamine or L-fucose neoglycolipids incorporated into phospholipid monolayers and liposome bilayers was studied at the air/water interface and in bulk solution. The results show that for both systems studied, synthesized neoglycolipids were capable of binding their specific lectin and that, in general, the binding of lectins increased with the increase in the molar fraction of the saccharide derivative incorporated in either the monolayers or bilayers. However, whereas for UEA-I, molecular recognition was enhanced by a strong hydrophobic interaction, for WGA and LTA successful recognition was predominantly related to the distance between neighboring sugar groups. The observed lengthy adsorption times of these lectins onto their specific ligands were attributed to interfacial conformational changes occurring in the proteins upon their adsorption at the interfaces.

The distribution and relative hydrolysis of tocopheryl acetate in the different matrices coexisting in the lumen of the small intestine during digestion could explain its low bioavailability

SCOPEnVitamin E is present in feed and food mainly as d-α-tocopherol (d-α-TOL) but also as all-rac-α-tocopheryl acetate (rac-α-TAC) through supplementation. Its absorption efficiency is low compared to that of triacylglycerols. The aim of this work was thus to study the fate of TAC during digestion.nnnMETHODS AND RESULTSnUsing an in vitro digestion model, we showed that TAC was distributed between mixed micelles (36%), liposomes (9%), and nonsolubilized food debris (52%). A significant fraction of TAC was also found in emulsions when fat hydrolysis was not complete. Among the candidate esterases tested, i.e. cholesteryl ester hydrolase, pancreatic lipase, and pancreatic lipase-related protein 2, only cholesteryl ester hydrolase was able to hydrolyze TAC to all-rac-α-TOL, about five times more efficiently when it was incorporated into mixed micelles or liposomes than into emulsions or in the food matrix. Caco-2 cells were able to hydrolyze TAC and to uptake TOL when TAC was incorporated into mixed micelles but not into emulsions.nnnCONCLUSIONnDuring digestion, most TAC is recovered in matrices where its hydrolysis and its uptake by intestinal cells are markedly less efficient than in mixed micelles.

Physical Aging of Progesterone-Loaded Poly(D,L,-lactide-co-glycolide) Microspheres

AbstractPurpose. To study the interactions between a polymeric matrix and a drug during storage at a temperature lower than the glass transition temperature of the polymers.nMethods. Poly(lactide-co-glycolide) microspheres loaded with different progesterone ratios were stored at 4, 20 and 40°C. DSC-scans were recorded at regular intervals, depending on the storage temperature.nResults. The physical aging of the polymeric matrix, as monitored by the amplitude of the endotherm associated with the glass transition, is slowed down by crystalline progesterone. The development of the progesterone polymorphic depends on the interface/volume ratio of the crystals.nConclusions. For polymeric drug delivery systems, the determination of all studies parameters must take into account an effect of dispersed drugs which are more sensitive as the storage temperature is lower than the glass transition temperature of the matrix.

Fucosyled neoglycolipids: synthesis and interaction with a phospholipid.

The interfacial behavior of the neoglycolipids formed of Guerbet alcohol (G(28)) bound to a triethylene glycol spacer (E(3)) and to a sugar moiety (alpha- and beta-fucose) spread at the air/water interface has been studied under dynamic conditions of compression. Although the alpha (alpha-FucE3G28)- and beta-fucose (beta-FucE3G28) derivatives possessed the same chemical structure, the positioning of the sugar moiety relative to the whole molecule had a significant influence on the organization of neoglycolipid molecules in the spread monolayers. Thus, beta-fucose molecules exhibited higher compressibilities and larger molecular areas than a alpha/beta (84/16%) mixture (alpha(84)-FucE3G28). The comparison of the compressional behavior of the fucose derivatives with that of Guerbet alcohol in the absence and in the presence of the triethylene glycol spacer shows that the presence of the E(3) chain is necessary to stabilize the lipid at the interface and that the incorporation of a sugar moiety into the molecule resulted in an important expansion of a monolayer. Despite their different interfacial behaviors, the two sugar derivatives formed ideal mixtures when cospread at the air/water interface. Conversely, in the presence of a phospholipid, such as DMPC, repulsive interactions were observed and appeared to be stronger for DMPC/alpha(84)-FucE3G28 mixed monolayers. The membrane fluidity of DMPC liposomes bearing the studied amphiphilic molecules was assessed by fluorescence depolarization measurements. The results reveal that whereas G(28) was deeply inserted into the liposome bilayers, the presence of a E(3) chain and of a sugar moiety in these bilayers induced a transfer of the amphiphilic derivatives from the hydrophobic core towards polar headgroups of phospholipid molecules.

Scale-up of nanoemulsion produced by emulsification and solvent diffusion.

The scale-up of nanoemulsions (NEs) produced by emulsification and solvent diffusion process was successfully achieved in the present work. Up to 1500 mL of NEs were produced with olive oil, castor oil, almond oil, or Arlamol™ E by using a Y-shaped mixer device. NE droplet sizes were significantly modulated from 290 to 185 nm by changing the process parameters without modification of the formulation composition. Smaller NE droplet sizes were obtained by (1) decreasing the internal diameter of the Y-mixer from 5 to 0.8 mm, (2) increasing the flow rates of the organic and the aqueous phases upon mixing, and (3) increasing the temperature of the experiment from 5°C to 40°C. All the results of NE diameters (d(sc) ) expressed as a function of the Reynolds number (Re) and the shear rate inside the Y-mixer (documentclass{article}usepackage{amssymb}begin{document}pagestyle{empty}

New Bicompartmental Structures Are Observed When Stearylamine is Mixed with Triglyceride Emulsions

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WETTABILITY OF DRUG LOADED POLYMER MATRICES

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Physico-chemical characterization of ethylcellulose drug-loaded cast films

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