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Biomedical subjects

J P Marty

Publications and source records attributed to J P Marty.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of skin viscoelasticity in type 1 neurofibromatosis patients.

Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant disease characterized by cutaneous benign tumors called neurofibromas. Surgery takes an important place in managing these skin disorders. However, skin distensibility and softness of NF1 patients quickly offset the surgical benefit. The aim of this study was to determine the rheological behavior of neurofibromas and compare it with healthy skin in an attempt to comprehend what leads to this phenomenon. Thirty patients were admitted to this study. A group of 24 healthy control subjects was also included. The skin elasticity was assessed by a noninvasive in vivo suction device (Cutometer) including 5 consecutive suctions. The assessments were performed on neurofibroma skin, the supposedly healthy skin around neurofibromas and the healthy skin of control subjects. The extensibility at the first and the fifth traction in NF1 patients (neurofibromas and the supposedly healthy skin around it) was significantly different compared to the healthy skin of control subjects. The viscoelastic parameters obtained from the neurofibromas were significantly different in comparison to those obtained from the supposedly healthy skin of NF1 patients and the healthy skin of control subjects. The rheological profiles of the neurofibromas and the apparent healthy skin of NF1 patients demonstrated a hyperextensibility behavior, but in neurofibromas, the skin was unable to return to its initial position at the end of the stretch.

Adolescent↗
PubMed2005

Percutaneous absorption of 4-cyanophenol from freshly contaminated soil in vitro: effects of soil loading and contamination concentration.

Despite the skin's excellent barrier function, dermal exposure to soil contaminated with toxic chemicals can represent a significant health hazard (e.g., via multiple work related contacts in the farming and waste disposal industries). The development of environmental standards or limits for chemical levels in soil has been impeded because quantification of percutaneous uptake from this medium has not been well-defined. The objective of the research described here, therefore, was to better characterize the rate and extent of dermal penetration as a function of soil loading and degree of soil contamination. The absorption of a model compound (4-cyanophenol, CP) across hairless mouse skin in vitro has been determined at four different soil loadings (5, 11, 38 and 148 mg cm-2) and at six levels of soil contamination (concentrations ranging from 0.19 to 38 mg/g soil). Following 8 h of exposure, the amount of CP absorbed was independent of soil loading when CP concentration was constant, implying that the quantity of soil presentwas always sufficientto provide atleast a single layer of tightly packed particles. At the lowest loadings, however, with increasing times of exposure, the CP transport rate fell off due to depletion of chemical from the soil. At constant soil loading (38 mg cm(-2)), CP flux (Jss) across the skin was linearly proportional to the level of contamination (C(o)soil) over the range 0.19 to 23.5 mg of CP per gram of soil: Jss (micorg cm(-2) h(-1)) = (1.1 x 10(-5) g cm(-2) h(-1)) x Csoil (microg/g soil). At the highest CP contamination concentration, however, the transport rate was about an order of magnitude higher than expected, possibly due to the presence of pure CP crystals. In conclusion, these results provide new quantifications of the characteristics of dermal uptake from chemically contaminated soils and important information with which to develop and verify predictive models of dermal absorption.

Administration, Cutaneous↗
PubMed2005

Rheological properties of three different vitamin D ointments and their clinical perception by patients with mild to moderate psoriasis.

BACKGROUND: Ointments, classically used for the treatment of dermatological diseases, are monophasic viscous semisolid formulations. According to the proportion of their compounds, they have physicochemical and organoleptic properties and when applied on skin show a specific behaviour allowing to be spread more or less easily. OBJECTIVE: To measure in vitro rheological characteristics of three vitamin D derivative ointments prescribed for the treatment of psoriasis, and to compare their viscosity and clinical acceptability when applied on the diseased skin. METHODS: Rheological characteristics of tacalcitol 4 microg/g, calcipotriol 50 microg/g and calcitriol 3 microg/g ointments were assessed by measuring the oscillatory viscoelastic parameters and the permanent flow analysis. Clinical acceptability was studied in 20 psoriatic male or female subjects, aged 18 years or older. A survey evaluated the acceptability of calcitriol vs. tacalcitol and calcipotriol. Questions included information about fluidity, spreading capacity and stickiness after application. RESULTS: We demonstrated that viscoelastic parameters were four times higher for ointment tacalcitol than for calcipotriol and calcitriol, corresponding to a higher consistency of ointment tacalcitol compared to calcipotriol and calcitriol showing both similar results; better fluidity was demonstrated by calcitriol than by tacalcitol and calcipotriol. Comparable results were obtained for the quality to be spread. The sensation of stickiness, significantly different between tacalcitol and calcitriol, was not different between calcipotriol and calcitriol. CONCLUSION: The above results confirm the relationship between rheological in vitro and sensorial in vivo results: variations between different formulations may have an important influence on non-adherence and treatment failure.

Administration, Cutaneous↗
PubMed2004

Release of antiseptics from the aqueous compartments of a w/o/w multiple emulsion.

A w/o/w multiple emulsion drug carrier system has been developed for local vaginal therapy. To improve its efficacy and to extend the antimicrobial spectrum activity of benzalkonium chloride (CBZ), which is introduced in the external aqueous phase, chlorhexidine digluconate (CHD) was added to the internal aqueous phase of the multiple emulsions. The minimal bactericidal concentrations (MBC) for the association of CHD and CBZ in emulsion were determined towards Escherichia coli and Staphylococcus aureus. The main release mechanism considered for the CHD encapsulated in the inner phase was a swelling-breakdown phenomenon which followed dilution of the emulsion under hypo-osmotic conditions. In order to demonstrate this release, the bactericidal effect of multiple emulsions undiluted and diluted 1-5 and 1-10 in hypo-osmotic conditions at two CHD concentrations was evaluated. To validate and quantify this release, rheological and release kinetics studies were used. The bactericidal activity of combination CBZ-CHD in the emulsion was synergistic on the two bacterial strains and the release of encapsulated CHD in the internal phase was obtained following its dilution in hypo-osmotic conditions. Vaginal administration could be carried out following dilution at 1-5 in sterile water for multiple emulsions containing the lower concentration of CHD.

Anti-Infective Agents, Local↗
PubMed2002

In vitro microbicidal activity of W/O/W multiple emulsion for vaginal administration.

The microbicidal activity of a W/O/W multiple emulsion destined for vaginal application, containing lactic acid in the internal aqueous phase, octadecylamine (ODA) in the oily phase and benzalkonium chloride (CBZ) in the external aqueous phase was evaluated against three microbial strains: Escherichia coli, Staphylococcus aureus and Candida albicans. The results were different depending on the procedure used. Interpretable results were obtained if only a gentle agitation was used just after the introduction of the microbial suspension to the product. This suggested that vigorous agitation lead to a variable fraction of CBZ or ODA entrapped in the micelles of ethylene and propylene oxide copolymer (COE).

Administration, Intravaginal↗
PubMed2001

Formulation of shear rate sensitive multiple emulsions.

This work mainly concentrates on the formulation of W/O/W multiple emulsions capable of breaking and releasing their inner aqueous phase under shear rates compatible with agroalimentary, pharmaceutical and cosmetic applications. Three kinds of multiple emulsions were studied: one with a high concentration of primary emulsion, not viscosified in the external aqueous phase; multiple emulsions gelified with a synthetic polymer (Carbopol 974P((R))); and other multiple emulsions thickened with chemically modified cellulose (hydroxypropylcellulose). The results of this study show the influence of the composition of the external aqueous phase of the emulsions on their fragmentation and release as a function of the shear rate. Despite these differences of behavior with respect to the shear rate, each emulsion fits to Taylor's theoretical framework, indicating that the bursting mechanisms of the globules under shear are the same whatever the composition of the multiple emulsions.

Chemistry, Pharmaceutical↗
PubMed2001

In vivo and in vitro percutaneous absorption of [(14)C]di-N-butylphthalate in rat.

This study evaluated the toxicokinetics of [(14)C]di-n-butylphthalate ([(14)C]DBP) after an intravenous administration (1 and 10 mg/kg, in Cremophor) or a topical application (10 microl/cm(2); 10 cm(2), neat) in haired male Sprague-Dawley rats. Additional in vivo and in vitro percutaneous penetration studies of [(14)C]DBP were conducted on male and female haired rats and male hairless rats. After intravenous administration, unchanged DBP disappeared rapidly from the plasma, following a two-exponential function (T1/2beta = 5-7 min). The peak levels of monobutylphthalate (MBP) and its glucuronide conjugate (MBP-Gluc) occurred 1 to 2 and 20 to 30 min after administration, respectively. These metabolites were intensively and rapidly excreted in urine (57% of the dose). However, about 35% of the dose recovered in urine was primarily excreted in bile (mainly as MBP-Gluc) and underwent hepatobiliary recycling. Unchanged DBP was barely detectable in excreta. DBP rapidly penetrated the skin, which constituted a reservoir. The absorption flux determined for 0.5 to 8 and 8 to 48 h of exposure were 43 and 156 microg/cm(2)/h, respectively. The higher flux may be due to radial diffusion of DBP in the stratum and/or epidermis. The in vivo and in vitro experiments revealed that DBP was intensively metabolized into the skin. In vivo percutaneous absorption flux was very similar in male and female haired rats. In contrast, the percutaneous absorption determined in vivo and in vitro was higher in hairless than in haired male rats. Absorption flux was accurately estimated from urinary excretion rate of MBP or MBP-Gluc.

Animals↗
PubMed2000

In vitro release of caffeine from concentrated W/O emulsions: effect of formulation parameters.

Concentrated water in oil emulsions have been obtained with four different emulsifiers to study the effect of formulation parameters on the in vitro release of caffeine. The in vitro release was studied on polysulfone membranes. Among the four emulsifiers, only one gave a statistically higher release of caffeine after 15 h (at a fixed percentage of dispersed phase). The concentration of the emulsifier does not have a significant effect on the release of caffeine. In contrast, diffusion of caffeine from concentrated W/O emulsions has been found to be highly dependent on the internal phase volume. The flux of caffeine increases with the percentage internal water phase. The droplet diameter decreases and the apparent viscosity increases with the percentage of the dispersed phase. And, the shape of the droplets goes from spherical to polyhedral as the percentage dispersed phase is increased. However, the flux could be correlated neither with the apparent viscosity nor with the droplet diameter at a fixed percentage of the dispersed phase. Results suggest that the shape factor may have an influence on the release of caffeine from concentrated emulsions. All the release profiles followed a zero-order kinetic.

Caffeine↗
PubMed2000

Influence of three synthetic membranes on the release of caffeine from concentrated W/O emulsions.

We measured the release rate characteristics of caffeine from concentrated emulsions using three different sources of synthetic membranes. The formulations tested included, on the one hand, two stable cosmetic concentrated W/O emulsions (90% w/w) - one with a non ionic surfactant and one with a silicone surfactant - and on the other hand, a commercially available hydroalcoholic gel. All formulations contained 5% caffeine. In vitro diffusion measurements (24 h) were performed with static diffusion Franz cells. A silicone membrane could not allow us to differentiate the two concentrated emulsions (CE), but the two other membranes, not rate limiting, showed difference in the release profile of caffeine from the two CE. Results with the cellulose and polysulfone membrane showed that in vitro release of caffeine is influenced by the nature of the emulsifier in the concentrated emulsion, the non ionic surfactant being more efficient than the silicone surfactant. The polysulfone membrane was the only one that allows statistical differentiation of the three products. For further studies the polysulfone membrane will be use to make screening on concentrated emulsions.

Caffeine↗
PubMed2000

[Efficiency of etidronic acid in the case of cutaneous radiocontamination by actinid elements: in vitro evaluation].

Ethane 1 hydroxy 1.1. biphosphonate (EHBP) is a medicine named Didronel, which inhibits bone resorption in the case of Paget's disease. This molecule could offer a new application in radiotoxicology. Our works describe its efficiency as decontaminating agent in uranium and plutonium cutaneous radiocontamination. Its effect on uranium and plutonium is demonstrated by two in vitro techniques using human cutaneous explants. Both techniques are usually used in dermopharmacology to estimate the action of topic drugs.

Chelating Agents↗
PubMed1999

Quantitative HPLC analysis of sunscreens and caffeine during in vitro percutaneous penetration studies.

This report describes rapid analytical HPLC for the quantification of five UV filters (octyl methoxycinnamate, benzophenone-3, benzophenone-4, octyl triazone and octocrylene) and of caffeine in various skin layers (stratum corneum, dermis, epidermis and receptor fluid) and in cosmetic preparations. The predominant purpose of the study was to establish standard operating procedures for rapid analysis of the compounds in various skin samples. Particular attention was paid to the preparation of biological samples whose natural constitution could interfere with the quantitative analysis. Our methods used the isocratic chromatographic mode in an RP-HPLC with UV detection and did not involve centrifugation or evaporation. Our results were validated in terms of specificity, linearity, precision, accuracy and limits of detection and quantification. The first results, obtained after in vitro experiments, are presented in this report.

Adolescent↗
PubMed1999

In vitro topical delivery of non-steroidal anti-inflammatory drugs through human skin.

The objective of the present study was to evaluate in vitro the percutaneous absorption, across human skin, of 5 non-steroidal anti-inflammatory drugs (NSAIDs) formulated as gels: ketoprofen (CAS 22071-15-4), epolamine diclofenac (CAS 15307-86-5), piroxicam (CAS 36322-90-4) and niflumic acid (CAS 4394-00-7) or as emulgel: diclofenac sodium (CAS 15307-79-6) and to compare the different formulations as drug delivery systems. Because the concentrations of the NSAIDs in the different excipients were not identical, the comparison of their diffusional properties was expressed in term of release efficiency (or diffusion efficacy). The results obtained show that, across human skin under standardized experimental conditions, ketoprofen and piroxicam have the best rank order followed by niflumic acid, diclofenac sodium and epolamine diclofenac.

Administration, Topical↗
PubMed1998

In vitro metabolism by human skin and fibroblasts of retinol, retinal and retinoic acid.

The metabolism of radio-labelled retinol, retinal and retinoic acid by fresh human skin as well as by human dermal fibroblasts have been investigated in vitro. Surgically removed human skin biopsies were placed at the air liquid interface, and treated topically for 24 h with retinoids. At the end of the treatment period, epidermis and dermis were separated by heat. Epidermis, dermis and medium were subsequently extracted and resulting fractions were analysed by HPLC. Dermal fibroblast cultures were treated and analysed in a comparable manner. Topical application of retinoids resulted in gradient concentrations within the skin. For each fraction, metabolites and unchanged product proportions were determined by HPLC. After treatment with retinol and retinal, low but significant amounts of retinoic acid were detected in the epidermis, as well as in the dermis (30 pmol to 90 pmol). In comparison, treatments with retinoic acid itself, led to higher level of retinoic acid in the epidermis and in the dermis (respectively 2050 and 420 pmol). Cultured human dermal fibroblasts, treated with retinol and retinal, formed retinoic acid as well as several other metabolites (retinol esters, reduction of retinal to retinol...). Taken together, our results are consistent with an action of retinol or retinal on the skin via a retinoic acid formation and a metabolic function of the dermis.

Administration, Topical↗
PubMed1998

Metabolism of 14C-moxisylyte after percutaneous application in hairless rat.

The pharmacokinetics of 14C-thymoxamine (4-(2-dimethylaminoethoxy)-5-isopropyl-2-methyl phenyl acetate, CAS 54-32-0, moxisylyte, Carlytène) were studied in female hairless rats following different administration routes: oral, intravenous or percutaneous. After percutaneous administration, the half-life of elimination of 14C-thymoxamine and its metabolites was longer (t 1/2 = 15 h) than after oral or intravenous administration (t 1/2 = 9 h). The penetration/resorption phenomenon of thymoxamine base mainly located in the horny layer could explain the high value of the pseudo half-life of elimination observed after percutaneous administration. Due to the absorption slower than elimination, this special pharmacokinetics had to be considered as a flip-flop model. The type and proportions of thymoxamine metabolites recovered in plasma varied according to the route of administration. The unconjugated metabolites, desacetyl-thymoxamine (DAT) + desacetyl-desmethyl-thymoxamine (DMAT), were observed only after intravenous or percutaneous administration, they represented 12% and 15%, respectively. They were never observed after oral administration suggesting the existence of a hepatic first-pass metabolism. The other metabolites observed were sulphate conjugates and glucuronides of DAT + DMAT. The values of sulfoconjugates were constant with each administration route (21%), whereas glucuronides increased with oral administration. In conclusion, the pharmacokinetics of percutaneous thymoxamine presented two main features: the drug absorption was high and durable (t 1/2 = 15 h); the cutaneous application allowed to avoid the hepatic first-pass metabolism.

Administration, Topical↗
PubMed1998

In vitro studies on the influence of carbomers on the availability and acceptability of estradiol gels.

The objective of the present study was to evaluate the pharmaceutical properties of estradiol (CAS 50-28-2) gels: pH, viscosity, texture, spreadability, evaporation of solvent and transcutaneous diffusion from carbomer-based formulations. This study was performed with the aim of measuring possible pharmaceutical differences as a function of the nature of the polymers used. The results obtained show a similarity of behaviour for the Estreva gels made with carbomers Carbopol 1342 (C 1342) and 1382 (C 1382). The reference gel, commercially available in France and made with the carbomer Carbopol 934 (C 934) is different in terms of its rheological criteria.

Acrylic Resins↗
PubMed1996

Menorest: technical development and pharmacokinetic profile.

Transdermal application of oestradiol enables the use of lower doses than with the oral drug and avoids first-pass metabolism in the liver. First-generation transdermal delivery systems were of reservoir design. Menorest is one of a new generation of patches, in which oestradiol is dispersed in a micronized suspension throughout the adhesive matrix. This design results in a very thin patch with good cosmetic acceptability. Pharmacokinetic studies indicate that Menorest allows transdermal release of oestradiol at a constant and reproducible rate at doses from 25-100 micrograms/day. There is a linear relationship between the dose of oestradiol administered (which is determined by the surface area of the patch) and the plasma concentration of oestradiol. In contrast to the standard reference reservoir patch, Estraderm, Menorest maintains plasma oestradiol concentrations at or above the target level of 40 pg/ml throughout the 84-h dosing interval.

Administration, Cutaneous↗
PubMed1996

New trends in transdermal technologies: development of the skin patch, Menorest.

Menorest is a transdermal patch, in which 17 beta-estradiol is dispersed as a microfine suspension in an adhesive matrix. This system reduces the size and thickness of the patch making it more cosmetically acceptable than older reservoir patches. Pharmacokinetic studies indicate that, at doses from 25-100 micrograms/day, Menorest releases estradiol at a constant and reproducible rate. There is a linear relationship between the dose of estradiol administered (which is determined by the surface area of the patch) and the plasma concentration of estradiol. Unlike the standard reference reservoir patch, Estraderm, or another matrix patch, Systen/Evorel, Menorest maintains plasma estradiol concentrations at or above the target level of 40 pg/ml throughout the 80-h dosing interval.

Administration, Cutaneous↗