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V Préat

Publications and source records attributed to V Préat.

At least 37 records · Page 2Linked to original sources
PubMed1998

Polymeric nanoparticles as delivery system for influenza virus glycoproteins.

The objective of this work was to develop a new delivery system which could enhance the mucosal immune response to influenza virus antigens. Poly(D,L-lactide-co-glycolide) nanoparticles of about 200 nm containing hemagglutinin were chosen as the delivery system. Due to the amphiphilic nature of hemagglutinin (hydrophilic HA1 and hydrophobic HA2), nanoparticles were prepared by both classical oil in water solvent evaporation technique as well as by a [(water-in-oil) in water] solvent evaporation technique. Hemagglutinin was well encapsulated in nanoparticles prepared by both techniques. Molecular weight and antigenicity of entrapped hemagglutinin were not affected by the entrapment procedure.

Animals↗
PubMed1998

In vitro percutaneous penetration through hairless rat skin: influence of temperature, vehicle and penetration enhancers.

Theoretically, a positive relation is expected between skin temperature and the percutaneous penetration of topically applied substances. The aim of the present study was to evaluate the influence of the temperature on the in vitro percutaneous penetration of dihydrotestosterone. Hairless rat skin was mounted in static diffusion cells placed in a water bath at different temperatures (28.6, 35.1 and 38.2 degrees C, respectively). Different vehicles were tested as well as the addition of penetration promoting molecules such as oleic acid and limonene. A saline buffer was used as the receptor phase. Penetration through the skin was evaluated by means of scintillation counting of the radiolabelled dihydrotestosterone. Experiments were followed for a period of 29 h. The total amount of penetrant, dihydrotestosterone, as well as the flux, were calculated from these kinetics. Our results demonstrate a temperature effect with the highest penetration at 38.2 degrees C. The vehicle was also found to influence the penetration of dihydrotestosterone in a significant way. Furthermore, limonene presented better penetration promoting properties compared with oleic acid.

Administration, Topical↗
PubMed1998

Localization of a FITC-labeled phosphorothioate oligodeoxynucleotide in the skin after topical delivery by iontophoresis and electroporation.

PURPOSE: The aim of this study was to verify the hypothesis that the application of high voltage to the skin enhances both stratum corneum and keratinocyte permeability. Therefore, the transport of FITC labelled phosphorothioate oligonucleotides (FITC-PS) administered by passive diffusion, iontophoresis or electroporation was localized. METHODS: Fluorescent microscopy and laser scanning confocal microscopy were used to visualize the FITC-PS transport at the tissue and cell level respectively in hairless rat skin after electroporation (5 x (200 V approximately 500 ms) or iontophoresis (same amount of charges transferred). RESULTS: FITC-PS did not penetrate the viable skin by passive diffusion. Molecular transport in the skin upon electroporation or iontophoresis was localized and implied mainly hair follicles for iontophoresis. In the stratum corneum, the pathways for FITC-PS transport were more transcellular during electroporation and paracellular during iontophoresis. FITC-PS were detected in the nucleus of the keratinocytes a few minutes after pulsing. In contrast, iontophoresis did not lead to an uptake of the oligomer. CONCLUSIONS: The internalization of FITC-PS in the keratinocytes after electroporation confirms the hypothesis and suggests that electroporation, which allows both efficient topical delivery and rapid cellular uptake of the oligonucleotides, might be useful for antisense therapy of epidermal diseases.

Administration, Topical↗
PubMed1998

Electroperturbation of human stratum corneum fine structure by high voltage pulses: a freeze-fracture electron microscopy and differential thermal analysis study.

Application of high voltage pulses (HVP) to the skin has been shown to promote the transdermal drug delivery by a mechanism involving skin electroporation. The aim of this study was to detect potential changes in lipid phase and ultrastructure induced in human stratum corneum by various HVP protocols, using differential thermal analysis and freeze-fracture electron microscopy. Due to the time involved between the moment the electric field is switched off and the analysis, only "secondary" phenomena rather than primary events could be observed. A decrease in enthalpies for the phase transitions observed at 70 degrees C and 85 degrees C was detected by differential thermal analysis after HVP treatment. No changes in transition temperature could be seen. The freeze-fracture electron microscopy study revealed a dramatic perturbation of the lamellar ordering of the intercellular lipid after application of HVP. Most of the planes displayed rough surfaces. The lipid lamellae exhibited rounded off steps or a vanished stepwise order. There was no evidence for perturbation of the corneocytes content. In conclusion, the freeze-fracture electron microscopy and differential thermal analysis studies suggest that HVP application induces a general perturbation of the stratum corneum lipid ultrastructure.

Electric Stimulation↗
PubMed1998

Parameters controlling topical delivery of oligonucleotides by electroporation.

Electroporation, using high voltage electrical pulses has been recognized as a powerful method for delivering macromolecules such as DNA and proteins in cells, or smaller molecules through the skin. Transdermal electroporation could combine targeted delivery of drugs to the skin and permeabilization of skin cells, suggesting that electroporation could be an interesting alternative for topical delivery of oligonucleotides. This work is devoted to the determination of the electroporation parameters that allow optimal delivery of oligonucleotides to the viable tissues of hairless rat skin in vitro. Phosphorothioate derivatives were preferred to the phosphodiester congeners as the former were found to be much less degraded when extracted from the tissues. Long duration (100-500 ms)--medium voltage (100-200 V)--exponentially decaying pulses appeared to be the best conditions for delivering oligonucleotides to the skin. The oligonucleotide quantity permeating the viable tissues of the skin was controlled by the selection of the electrical parameters of the pulses (voltage, pulse time and number of pulses) or by the ON concentration in the donor compartment. After delivery by electroporation, therapeutic levels of oligonucleotides were reached in the viable tissues of the skin (above 1 microM or 10 microM in intact or stripped skin respectively). Taken together, our results show that electroporation could be an interesting method for the delivery of oligonucleotides to the skin.

Administration, Cutaneous↗
PubMed1997

Macromolecules as novel transdermal transport enhancers for skin electroporation.

PURPOSE: Macromolecules were investigated as chemical enhancers of transdermal transport by skin electroporation. Although unable to enhance passive or iontophoretic transport, macromolecules are proposed to enhance electroporation-assisted delivery by stabilizing the increased permeability caused by high-voltage pulses. METHODS: To test this hypothesis, we examined the timescale of transport, the influence of electrical protocol and the influence of macromolecule size, structure, and charge on enhancement of transdermal mannitol transport in vitro by heparin, dextran-sulfate, neutral dextran, and poly-lysine. RESULTS: Skin electroporation increased transdermal mannitol delivery by approximately two orders of magnitude. The addition of macromolecules further increased transport up to five-fold, in support of the proposed hypothesis. Macromolecules present during pulsing enhanced mannitol transport after pulsing for hours, apparently by a macromolecule-skin interaction. No enhancement was observed during passive diffusion or low-voltage iontophoresis, suggesting that macromolecules interact specifically with transport pathways created at high voltage. Although all macromolecules studied enhanced transport, those with greater charge and size were more effective. CONCLUSIONS: This study demonstrates that macromolecules can be used as transdermal transport enhancers uniquely suited to skin electroporation.

Administration, Cutaneous↗
PubMed1996

Transdermal permeation of alniditan by iontophoresis: in vitro optimization and human pharmacokinetic data.

PURPOSE: The aim of this paper was to assess the feasibility of electrically enhanced transdermal delivery of alniditan, a novel 5 HT1D agonist for the treatment of migraine. METHODS: An in vitro study was first performed to optimize the different parameters affecting iontophoresis efficiency. The mechanism of alniditan permeation by iontophoresis was investigated. Finally, a phase I clinical trial was performed to assess systemic delivery of alniditan by iontophoresis. RESULTS: i) In vitro: The optimal conditions were found with a buffer like ethanolamine at a pH of 9.5, with Ag/AgCl electrodes and a direct current application. Alniditan permeation was enhanced when increasing the current density, the duration of current application and the drug concentration. Iontophoresis slightly increased drug quantities in stratum corneum compared to passive diffusion but it strongly increased alniditan quantities in viable skin. ii) The objective to deliver in vivo 0.5 mg of alniditan within less than 1 h was reached but an erythema was detected at the anode. CONCLUSIONS: This study demonstrates the feasibility of iontophoretic delivery system for antimigraine compounds.

Administration, Cutaneous↗
PubMed1996

Transdermal delivery of fentanyl by electroporation. II. Mechanisms involved in drug transport.

PURPOSE: The aim of the present report was to systematically analyze the mechanisms involved in fentanyl transdermal transport by skin electroporation. METHODS: The study was performed in vitro with full-thickness hairless rat skin, skin electroporation being carried out with five exponentially-decaying pulses of 100 V applied voltage and around 600 ms pulse duration. RESULTS: Transport during and after pulsing are both important in transdermal delivery of fentanyl by skin electroporation. Rapid transport occurred during pulsing due to electrophoresis and diffusion through highly permeabilized skin. No electroosmosis was observed. The slow post-pulse passive transport was explained by lasting changes in skin permeability. Measurements of fentanyl quantities in the skin demonstrated that pulses rapidly loaded the viable part of the skin with fentanyl and hence rapidly overcame skin barrier. CONCLUSIONS: The different contributions of the transport mechanisms appear to depend on the physicochemical parameters of the transported molecule as well as the solution, suggesting that mechanistic analysis and careful consideration of formulation variables are essential for the development and optimization of drug delivery by skin electroporation.

Administration, Cutaneous↗
PubMed1996

Transdermal delivery of fentanyl by electroporation. I. Influence of electrical factors.

PURPOSE: Electroporation, a method of reversibly permeabilizing lipid bilayers by the application of an electric pulse, has been shown to induce increased transdermal passage of molecules. The aim of the present report was to study in vitro with hairless rat skin the potential of electroporation for transdermal delivery of fentanyl. RESULTS: The application of electric pulses can strongly promote transdermal delivery of fentanyl compared to passive diffusion through untreated skin. We also point out that the choice of the waveform of the electric pulses is important: at the same applied energy, a few exponentially-decaying (ED) pulses increased fentanyl permeation more than a few square-wave pulses and to the same extent as the repeated application of higher voltage-shorter duration ED pulses. A factorial design showed that the voltage, duration, and number of ED pulses allowed control of the quantity of drug transported through the skin. CONCLUSIONS: Skin electroporation could be a good way to improve the transdermal diffusion of fentanyl.

Analgesics, Opioid↗
PubMed1995

Noninvasive investigation of human skin after in vivo iontophoresis.

The main objective of our study was to investigate skin function and structure in human volunteers after electrical current application in order to demonstrate the safety of iontophoresis in vivo. The direct current was applied for 30 min at a density of 0.1 and 0.2 mA/cm2. Iontophoresis increased cutaneous blood flow as measured by laser Doppler flowmetry (LDF). This increase was reversible within 1 h and was more pronounced at higher current density. Measurements of transepidermal water loss (TEWL) and LDF were the same at the cathode and the anode sites. Except for 5 min at 0.2 mA/cm2 density, TEWL values were not enhanced as compared to control values (no iontophoresis). Attenuated total reflectance-Fourier transform infrared spectroscopy of the stratum corneum structure showed a transient increase (30 min) in hydration after electrode application for 30 min. No alteration in lipid structure could be shown. These results augur the safety of drug delivery by iontophoresis.

Adult↗
PubMed1994

Transdermal delivery of metoprolol by electroporation.

Electroporation, i.e., the creation of transient "pores" in lipid membranes leading to increased permeability, could be used to promote transdermal drug delivery. We have evaluated metoprolol permeation through full thickness hairless rat skin in vitro following electroporation with an exponentially decaying pulse. Application of electric pulses increased metoprolol permeation as compared to diffusion through untreated skin. Raising the number of twin pulses (300 V, 3 ms; followed after 1 s by 100 V, 620 ms) from 1 to 20 increased drug transport. Single pulse (100 V, 620 ms) was as effective as twin pulse application (2200 V, 1100 V or 300 V, 3 ms; followed after 1 s by 100 V, 620 ms). In order to investigate the effect of pulse voltage on metoprolol permeation, 5 single pulses (each separated by 1 min) were applied at varying voltages from 24 to 450 V (pulse time 620 ms). A linear correlation between pulse voltage and cumulative metoprolol transported after 4 h suggested that voltage controls the quantity of drug delivered. Then, the effect of pulse time on metoprolol permeation was studied by varying pulse duration of 5 single 100 V pulses from 80 to 710 ms (each pulse also separated by 1 min). Cumulative metoprolol transported after 4 h increased linearly with the pulse time. Therefore, pulse time was also a control factor of the quantity of drug delivered but to a lesser extent than the voltage at least at 100 V.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1994

Human calcitonin delivery in rats by iontophoresis.

In-vitro ionotophoresis (0.33 mA cm-2) of calcitonin (50 micrograms mL-1, pH 4) was performed with the hairless rat skin model. Direct current was as potent as pulse current (2.5 kHz on/off 1/1) iontophoresis in promoting transdermal permeation of calcitonin. Increase in duration of current application from 20 min to 1 h did not increase calcitonin flux. Results suggest that calcitonin can be blocked in the skin pores through which it travels or can accumulate in the skin and be progressively released from the depot. In-vivo experiments showed that transdermal iontophoretic administration of calcitonin induced a hypocalcaemic effect in rats.

Animals↗
PubMed1993

In vivo iontophoresis of fentanyl and sufentanil in rats: pharmacokinetics and acute antinociceptive effects.

Iontophoresis is a process which enhances skin permeation of ionized species by using an electrical field as driving force. The aim of the present study was to investigate whether transdermal iontophoresis of fentanyl or sufentanil could induce therapeutic plasma levels and antinociceptive effect. Fentanyl and sufentanil were introduced in an acidic buffer (acetate buffer 0.01 M at pH 5) at 40 micrograms/mL. A platinum electrode was clamped in an hydrophilic foam soaked with the drug solution and linked to the anode. A cathodic foam reservoir was filled with saline solution. The device was applied on the abdominal skin of hairless rats and direct current (0.17 mA/cm2) was applied for 1 h. Opioid plasma concentrations were monitored. In the experimental conditions used, iontophoresis strongly increased transdermal permeation of the drugs as compared to diffusion. A 1.5 h Tmax was observed. The maximal plasma levels after 1.5 h were 29.3 +/- 14 ng/mL for fentanyl and 29.1 +/- 14 ng/mL for sufentanil. The plasma level of the narcotics decreased slowly after iontophoresis was terminated. Iontophoretic transdermal permeation of fentanyl and sufentanil in rats induced analgesic effects as measured by the tail-flick test. These effects lasted for about 4 h. Thus, transdermal iontophoresis with a miniaturized device is effective for the controlled and pulsatile or sustained delivery of synthetic opiates for pain management in humans. As compared to classical patches, it could reduce the lag time before reaching steady state and allow variable drug release rate.

Administration, Cutaneous↗
PubMed1992

Factors affecting iontophoretic mobility of metoprolol.

The effect of different factors on the iontophoretic transport of metoprolol was analyzed. In vitro experiments were first performed in a diffusion cell with a cellophane membrane. Comparison of different pH, buffers, and ionic strengths in the donor compartment showed that higher iontophoretic transport was obtained with phthalate buffer (0.01 M) at pH 3. When the current density increased, the flux of metoprolol also increased. A decrease in drug concentration or an increase in viscosity slowed down the iontophoretic transport of metoprolol. The fluxes of metoprolol through hairless rat skin were strongly enhanced compared with passive diffusion. Direct current seemed to be more efficient than pulse current. When the on:off ratio of the pulse current was reduced, the flux also decreased.

Algorithms↗
PubMed1992

Macrophage activation by polymeric nanoparticles of polyalkylcyanoacrylates: activity against intracellular Leishmania donovani associated with hydrogen peroxide production.

Nanoparticles of polyalkylcyanoacrylates (PACA) can be useful carrier for the targeting of antileishmanial drugs into macrophages and also possess significant antileishmanial activity by themselves. No significant difference in antileishmanial activity could be detected between nanoparticles of five PACAs with differing alkyl side chains, suggesting that the main degradation products of PACA are not involved in their antileishmanial action. The effect of polyisohexylcyanoacrylate (PIHCA) on the induction of the respiratory burst in a macrophage-like cell line (J774G8) was assessed in non-infected macrophages and in macrophages infected with amastigotes of Leishmania donovani infantum, by measuring nitroblue tetrazolium (NBT) reduction and hydrogen peroxide production. Phagocytosis of PIHCA nanoparticles led to a respiratory burst, which was more pronounced in infected than in uninfected macrophages. The production of reactive oxygen intermediates associated with the respiratory burst was inhibited by addition of superoxide dismutase and catalase to the cell suspensions. The addition of catalase to the culture medium together with PIHCA nanoparticles significantly reduced the antileishmanial activity of PIHCA. Moreover PIHCA nanoparticles did not induce interleukin-1 release by macrophages. It is suggested that the antileishmanial action of PIHCA and other PACA nanoparticles results from the activation of respiratory burst in macrophages.

Animals↗
PubMed1992

Drug targeting with polyalkylcyanoacrylate nanoparticles: in vitro activity of primaquine-loaded nanoparticles against intracellular Leishmania donovani.

The efficacy of primaquine-loaded polyisohexylcyanoacrylate (PIHCA) nanoparticles was evaluated using J774G8 macrophage-like cells infected with Leishmania donovani: as an in vitro model of visceral leishmaniasis. The in vitro antileishmanial activity of primaquine-loaded nanoparticles showed a 21-fold increase in ED50 compared with free primaquine. Although unloaded PIHCA nanoparticles also exhibited a significant anti-leishmanial effect, the loaded nanoparticles showed a synergistic effect compared with a mixture of unloaded nanoparticles and free primaquine at equivalent concentrations. Primaquine release and isohexanol production were evaluated in a lysosomal fraction; the correlation of both with protein concentration and the rapid drug release indicate the processes are associated with an enzymatic degradation. The results indicate that PIHCA and other polyalkylcyanoacrylates may be useful for targeting drugs at intracellular Leishmania, and that the unloaded carrier itself could be of interest in experimental chemotherapy of leishmaniasis.

Animals↗
PubMed1992

Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis in portacaval shunted rats.

Hepatocarcinogenesis was initiated in rats with diethylnitrosamine (DEN) followed by a selection with 2-acetylamino-fluorene (2-AAF). Portacaval shunt was then performed in order to promote tumor development. Control rats were not submitted to the initiation--selection protocol and were sham-operated. In control rats, adenylate cyclase activity from crude liver membranes was stimulated 7- to 8-fold by maximal doses of glucagon (10(-6) M) or guanyl-5'-yl-imidophosphate [Gpp(NH)p] (10(-3) M), and 17-fold by a maximal (10(-5) M) dose of forskolin. Guanosine-5'-O-(2-thiodiphosphate) inhibited the response to forskolin (-38%) and to low doses of glucagon (-50%). The initiation--selection protocol increased the activity in basal conditions and in response to various stimuli. The portacaval shunt did not modify the activity of the enzyme with respect to basal activity or the response to glucagon. It significantly decreased the response to Gpp(NH)p (-45%) and to forskolin (-27%). The initiation--selection protocol increased the basal activity of the enzyme (+150%) and its response to Gpp(NH)p (+300%). When tumors developed, the activity of the cyclase further increased (+200%) and an inhibitory effect of GTP on the hormone-stimulated enzyme appeared (-40%). From these results, it is concluded that the promotion of hepatocarcinogenesis by portacaval shunt is coupled with modifications in the activity of adenylate cyclase in response to glucagon and guanylnucleotides.

2-Acetylaminofluorene↗