Release of liposomes from hyaluronic acid-based hybrid systems: effects of liposome surface and size.

Mixtures of hyaluronic acid (HA, in the semi-dilute entangled regime) with liposomes (high lipid concentration) exhibit a great interest in drug delivery. Considering the difference of microstructures when varying the liposome surface, we aimed to determine if liposome characteristics (surface and size) also influenced their release from these hybrid systems and to explore the mechanisms involved. Small-angle neutron scattering, cryogenic electron microscopy, zetametry, and dynamic light scattering were used to characterize liposomes.

An injectable, nanostructured implant for the delivery of adenosine triphosphate: towards long-acting formulations of small, hydrophilic drugs.

While long-acting injectable treatments are gaining increasing interest in managing chronic diseases, the available drug delivery systems almost exclusively rely on hydrophobic matrixes, limiting their application to either hydrophobic drugs or large and hydrophilic molecules such as peptides. To address the technological lock for long-acting delivery systems tailored to small, hydrophilic drugs such as anticancer and antiviral nucleoside/nucleotide analogues, we have synthesized and characterized an original approach with a multi-scale structure: (i) a nucleotide (adenosine triphosphate, ATP) is first incorporated in hydrophilic chitosan-Fe(III) nanogels; (ii) these nanogels are then transferred by freeze-drying and resuspension into a water-free, hydrophobic medium containing PLGA and an organic solvent, N-methyl-2-pyrrolidone. We show that this specific association allows an injectable and homogeneous dispersion, able to form in situ implants upon injection in physiological or aqueous environments.

Biomaterial-embedded extracellular vesicles improve recovery of the dysfunctional myocardium.

Extracellular vesicles (EV) are increasingly recognized as a therapeutic option in heart failure. They are usually administered by direct intramyocardial injections with the caveat of a rapid wash-out from the myocardium which might weaken their therapeutic efficacy. To improve their delivery in the failing myocardium, we designed a system consisting of loading EV into a clinical-grade hyaluronic acid (HA) biomaterial.

Hybrid systems combining liposomes and entangled hyaluronic acid chains: Influence of liposome surface and drug encapsulation on the microstructure.

Mixtures of hyaluronic acid (HA) with liposomes lead to hybrid colloid-polymer systems with a great interest in drug delivery. However, little is known about their microstructure. Small angle neutron scattering (SANS) is a valuable tool to characterize these systems in the semi-dilute entangled regime (1.

Transtympanic injection of a liposomal gel loaded with N-acetyl-L-cysteine: A relevant strategy to prevent damage induced by cochlear implantation in guinea pigs?

Patients with residual hearing can benefit from cochlear implantation. However, insertion can damage cochlear structures and generate oxidative stress harmful to auditory cells. The antioxidant N-acetyl-L-cysteine (NAC) is a precursor of glutathione (GSH), a powerful endogenous antioxidant.

Extracellular Vesicles and Biomaterial Design: New Therapies for Cardiac Repair.

There is increasing evidence that extracellular vesicles (EVs) mediate the paracrine effects of stem cells. Although EVs have several attractive characteristics, they also raise issues related to delivery. For patients with cardiac disease that require a surgical procedure, direct intramyocardial (IM) administration of EVs is straightforward but its efficacy may be limited by fast wash-out, hence the interest of incorporating EVs into a controlled release polymer to optimize their residence time.

Nanocarriers for drug delivery to the inner ear: Physicochemical key parameters, biodistribution, safety and efficacy.

Despite the high incidence of inner ear disorders, there are still no dedicated medications on the market. Drugs are currently administered by the intratympanic route, the safest way to maximize drug concentration in the inner ear. Nevertheless, therapeutic doses are ensured for only a few minutes/hours using drug solutions or suspensions.

Controlled delivery of follicle-stimulating hormone in cattle.

Embryo transfer in cattle is a key issue requiring in vivo production of several mature follicles as opposed to the normal production of only one. In vivo produced embryos can then be transferred to recipient cows for gestation to occur. To obtain a large number of transferable embryos, the superovulation step is crucial.

Assessment of the efficacy of a local steroid rescue treatment administered 2 days after a moderate noise-induced trauma in guinea pig.

Objectives: Intratympanic injection of corticosteroids membrane after noise-induced hearing loss is an accepted alternative to general administration. We investigated the effect on hearing of a hyaluronic acid gel with liposomes loaded with dexamethasone (DexP) administered into the middle ear.

Methods: An acute acoustic trauma was performed to 13 guinea pigs for a period of 1 h on Day -2.

Mixtures of hyaluronic acid and liposomes for drug delivery: Phase behavior, microstructure and mobility of liposomes.

Hyaluronic acid liposomal gels have previously demonstrated in vivo their great potential for drug delivery. Elucidating their phase behavior and structure would provide a better understanding of their use properties. This work evaluates the microstructure and the phase behavior of mixtures of hyaluronic acid (HA) and liposomes and their impact on the vesicle mobility.

Thirty years with cyclodextrins.

This paper reviews the work carried out on cyclodextrins during some thirty years at the Institut Galien Paris-Sud, UMR CNRS 8612, Université Paris-Sud. It represents the normal evolution of this domain of science and the numerous possibilities of cyclodextrins for being a tool adaptable to the most complex situations. The works which have been carried out concern: the investigation of general characteristics of cyclodextrins and derivatives, the preparation and evaluation of inclusion complexes, the use of cyclodextrins in the preparation of drug delivery systems, the various possibilities offered by cyclodextrins and their derivatives for nanoparticle preparation and finally the use of cyclodextrins for the preparation of biomaterials is evoked.

Effect of a liposomal hyaluronic acid gel loaded with dexamethasone in a guinea pig model after manual or motorized cochlear implantation.

Goals of cochlear implantation have shifted from complete insertion of the cochlear electrode array towards low traumatic insertion with minimally invasive techniques. The aim of this study was first to evaluate, in a guinea pig model of cochlear implantation, the effect of a motorized insertion technique on hearing preservation. The second goal was to study a new gel formulation containing dexamethasone phosphate loaded in liposomes (DEX-P).

Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear.

The inner ear is one of the most challenging organs for drug delivery, mainly because of the blood-perilymph barrier. Therefore, local rather than systemic drug delivery methods are being developed for inner ear therapy. In this work, we have evaluated the benefit of a hyaluronic acid liposomal gel for sustained delivery of a corticoid to the inner ear after local injection into the middle ear in a guinea pig model.

Recent advances in local drug delivery to the inner ear.

Inner ear diseases are not adequately treated by systemic drug administration mainly because of the blood-perilymph barrier that reduces exchanges between plasma and inner ear fluids. Local drug delivery methods including intratympanic and intracochlear administrations are currently developed to treat inner ear disorders more efficiently. Intratympanic administration is minimally invasive but relies on diffusion through middle ear barriers for drug entry into the cochlea, whereas intracochlear administration offers direct access to the colchlea but is rather invasive.

Effect of liposomes on rheological and syringeability properties of hyaluronic acid hydrogels intended for local injection of drugs.

The aim of this work was to thoroughly study the effect of liposomes on the rheological and the syringeability properties of hyaluronic acid (HA) hydrogels intended for the local administration of drugs by injection. Whatever the characteristics of the liposomes added (neutral, positively or negatively charged, with a corona of polyethylene glycol chains, size), the viscosity and the elasticity of HA gels increased in a lipid concentration-dependent manner. Indeed, liposomes strengthened the network formed by HA chains due to their interactions with this polymer.

Adsorption of antisense oligonucleotides targeting malarial topoisomerase II on cationic nanoemulsions optimized by a full factorial design.

Cationic nanoemulsions have been recently considered as potential delivery systems for oligonucleotides (ON) targeting Plasmodium falciparum topoisomerase II gene. This study is aiming to select the best composition of nanoemulsions intended to ON adsorption by means of a 2(3) full factorial design. Based on their physicochemical properties, two formulations were selected for further studies, both composed by medium chain triglycerides, egg-lecithin, and either oleylamine (OA) or 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP).

Oil-cyclodextrin based beads for oral delivery of poorly-soluble drugs.

The main interest of cyclodextrins results from their ability to form inclusion complexes with hydrophobic molecules. This property is employed in pharmaceutical industry to facilitate the formulation of poorly-soluble and/or fragile drugs. Cyclodextrins are also used to form or stabilise dispersed systems.

Drug-induced nanocarrier assembly as a strategy for the cellular delivery of nucleotides and nucleotide analogues.

The natural nucleotide adenosine triphosphate (ATP) and nucleotide analogues such as azidothymidine triphosphate (AZT-TP) display important pharmacological activities for the treatment of ischemia and HIV infections, respectively. Their clinical use is, however, limited mostly due to their hydrophilicity, which highly restricts their diffusion into the target cells. Few nanocarriers have been proposed to address the challenge of ATP/AZT-TP cellular delivery, but the loading efficiency, preparation complexity, and efficient cellular delivery remain important barriers to their development.

Beads made of α-cyclodextrin and soybean oil: the drying method influences bead properties and drug release.

Freeze-dried beads made of α-cyclodextrin and soybean oil were reported previously as an efficient system for the oral delivery of lipophilic drugs. In the present study, oven-drying was evaluated as another method for drying beads. Oven-drying was optimised and the properties of the resulting beads were assessed.

Hyaluronic acid-bearing lipoplexes: physico-chemical characterization and in vitro targeting of the CD44 receptor.

The mechanism by which hyaluronic acid (HA)-bearing lipoplexes target the A549 lung cancer cell line was evaluated. For this purpose, cationic liposomes targeting the CD44 receptor were designed thanks to the incorporation in their composition of a conjugate between high molecular weight HA and the lipid DOPE (HA-DOPE). Liposomes containing HA-DOPE were complexed at different lipids:DNA ratios with a reporter plasmid encoding the green fluorescent protein (GFP).

Formulations based on alpha cyclodextrin and soybean oil: an approach to modulate the oral release of lipophilic drugs.

The purpose of this work was to investigate the potential of α-cyclodextrin combined to soybean oil-based formulations to modulate the release of a model drug, indomethacin. Dry emulsion, naked and coated beads were prepared from the same initial formulation using the same manufacturing process. Dry emulsion was selected to accelerate drug release while beads coated with α-cyclodextrin were designed to sustain it.

Liposomes for intravitreal drug delivery: a state of the art.

Intravitreal administration of drugs has raised a large interest during the last two decades improving the treatment of infectious diseases of the posterior segment of the eye or edematous maculopathies. This route of administration allows achieving high drug concentrations in the vitreous and avoiding adverse effects resulting from systemic administration. However, many drugs are rapidly cleared from the vitreous humor; therefore, to reach and to maintain effective therapy, repeated administrations are necessary.

[Potential of liposomes for the intravitreal injection of therapeutic molecules].

Intravitreal administration has been widely used since 20 years and has been shown to improve the treatment of diseases of the posterior segment of the eye with infectious origin or in edematous maculopathies. This route of administration allows to achieve high concentration of drug in the vitreous and avoids the problems resulting from systemic administration. However, two basic problems limit the use of intravitreal therapy.

Beads made of cyclodextrin and oil for the oral delivery of lipophilic drugs: in vitro studies in simulated gastro-intestinal fluids.

The aim of this work was to investigate the stability in vitro, in simulated gastro-intestinal fluids, of beads, made of α-cyclodextrin and soybean oil, and to study the release of progesterone, a model of lipophilic drug. This was evaluated over time by the monitoring of the proportion of intact beads, their volume and the percentage of progesterone dissolved. Their incubation in the simulated gastric fluid provoked a moderate reduction of their number (20%) and a decrease of their volume (50%) after 55 min.

Cationic nanoemulsion as a delivery system for oligonucleotides targeting malarial topoisomerase II.

A promising strategy based on the antisense oligonucleotides against the Plasmodium falciparum topoisomerase II has been considered using cationic nanoemulsion as oligonucleotide delivery system. Phosphodiester and chemically modified phosphorothioate oligonucleotides bearing negative charges were adsorbed on positively charged emulsion composed of medium chain triglycerides, egg lecithin, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and water, at different +/- charge ratios (positive charges from cationic lipid/negative charges from oligonucleotide): +0.5/-, +2/-, +4/- and +6/-.