Transdermal drug delivery by skin electroporation in the rat.

Drug delivery across skin offers advantages over conventional modes of administration. It avoids gastrointestinal degradation and the hepatic first-pass effect, has potential for controlled and sustained delivery, is user-friendly and therefore improves patient compliance (1-2). However, because the skin's outer layer, the stratum corneum, is an extremely effective barrier, transdermal transport of most drugs is very slow, exhibits lag times of hours and steadystate rates that are often subtherapeutic.

Intranasal immunization against influenza virus using polymeric particles.

The aim of this study was to evaluate the potential of poly(D,L-lactide-co-glycolide) nano-and microspheres, with a mean diameter of 220 nm and 8 microm, respectively, to enhance the nasal and systemic immune responses against influenza virus antigen. High encapsulation levels of antigen were achieved in all cases. Neither the molecular weight nor the antigenicity of the entrapped antigen were affected by the encapsulation procedure.

Mechanisms of a phosphorothioate oligonucleotide delivery by skin electroporation.

Skin electroporation has great potential for topical delivery of oligonucleotides. Controled therapeutic levels of an intact phosphorothioate oligonucleotide (PS) can be reached in the viable tissue of the skin. The aim of this work was to investigate the transport mechanisms of a PS in hairless rat skin by electroporation, and hence to allow optimization of oligonucleotides (ONs) topical delivery.

Comparison of the effects of short, high-voltage and long, medium-voltage pulses on skin electrical and transport properties.

High-voltage pulses have been shown to increase rates of transport across skin by several orders of magnitude on a time scale of minutes to seconds. Two main pulse protocols have been employed to promote transport: the intermittent application of short ( approximately 1 ms) high-voltage (approximately 100 V across skin) pulses and a few applications of long (=100 ms) medium-voltage (>30 V across skin) pulses. In order to better evaluate the benefits of each protocol for transdermal drug delivery, we compared these two protocols in vitro in terms of changes in skin electrical properties and transport of sulforhodamine, a fluorescent polar molecule of 607 g/mol and a charge of -1.

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.

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).

Transdermal alniditan delivery by skin electroporation.

The aim of this study was to evaluate the transdermal permeation of alniditan by electroporation and to compare with iontophoretic delivery. The influence of the electrical parameters of electroporation was investigated in vitro using a factorial design study. The transdermal flux of alniditan was enhanced by two orders of magnitude by application of high voltage electrical pulses.

Transdermal permeation of neutral molecules by skin electroporation.

Electroporation of skin has recently been shown to enhance transport of charged molecules across skin by up to four orders of magnitude. This study demonstrates that high-voltage pulses can also increase transdermal permeation of two neutral model solutes, i.e.

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.

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.

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.

Transdermal delivery of fentanyl: rapid onset of analgesia using skin electroporation.

Skin electroporation has recently been shown to increase transdermal transport of small-size drugs as well as considerably larger molecules by up to 4 orders of magnitude in vitro. Nevertheless, no in vivo studies have proven that high-voltage pulses can induce therapeutic plasma levels of drug. The aim of the present report was precisely to study the potential of skin electroporation in transdermal delivery of fentanyl in vivo.

In vivo noninvasive evaluation of hairless rat skin after high-voltage pulse exposure.

Short high-voltage pulses have recently been shown to dramatically increase and expedite transdermal drug transport via a mechanism hypothesized to involve electroporation. This study addresses tolerance issues of the method in vivo in hairless rat. Chromametry, transepidermal water loss (TEWL), laser Doppler flowmetry (LDF) and corneometry were jointly used for noninvasive sensing of skin biophysical parameters.

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.

Stability study of nanoparticles of poly(epsilon-caprolactone), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide).

The objective was to evaluate the stability of nanoparticles prepared with poly(epsilon-caprolactone), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers and stored at different temperatures and in different media. The stability parameters studied were molecular weight and crystallinity of the polymer, nanoparticle size and pH. The results show that the stability of polymeric nanoparticles depends on (i) the type of polymers with the following increasing order of polymer stability: PLA25GA50 < PLA37.

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.

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.

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.

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.

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.

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.

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.

[Clinical formulations of amphotericin B].

The clinical use of amphotericin B is impaired by its poor water solubility and by the severity of its side effects. Several amphotericin B formulations have already been prepared in an attempt to overcome these disadvantages. The following methods have been proposed to solubilize amphotericin B in water: the complexation of amphotericin B with metallic ions, sodium tetraborate or gamma cyclodextrin or the synthesis of semi-synthetic derivatives.

Comparison of nephrotoxicities of different polyoxyethyleneglycol formulations of amphotericin B in rats.

The aim of the present study was to assess whether amphotericin B (AmB)-Myrj 59, AmB-polyoxyethyleneglycol 24 cholesterol (PC), and AmB-Synperonic A50 (SA50) were less nephrotoxic than AmB-deoxycholate (DC). Rats were treated with the different AmB formulations (10 mg/kg of body weight) intraperitoneally or with the surfactants alone. A group of control rats receiving the vehicle was also examined.