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Biomedical subjects

M Seiller

Publications and source records attributed to M Seiller.

At least 19 recordsLinked to original sources
PubMed2006

[Drug delivery systems: a real therapeutic advance].

Established at the request of the Research Committee of the French National Academy of Pharmacy, this report on drug delivery systems (DDS) is a summary of information gathered by interviewing leaders in the pharmaceutical community and from the international literature. This report includes: a rapid recall of pharmaceutical formulations and changes over the last decades; a definition of DDS, indications on their evolution and a discussion on their contribution to drug administration; information on firms specialized in the elaboration of DDS, their interactions with the drug industry and the current and future market for DDS; a presentation of the potential offered by DDS for the drug industry; a discussion on technical, regulatory, and economic issues which could obstruct drug administration using a DDS; a description of certain DDS selected for their therapeutic contributions and a brief presentation of perspectives; a presentation of certain recommendations for organizations concerned with DDS.

Animals↗
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

Absorption and efficiency of insulin after oral administration of insulin-loaded nanocapsules in diabetic rats.

Poly(isobutylcyanoacrylate) nanocapsules have been shown to decrease the blood glucose level after oral administration to streptozotocin-induced diabetic fasted rats after 2 days [Diabetes 37 (1988) 246]. Yet, the absorption of insulin in the blood of rats has not been characterised. The aim of this work was to evaluate the biological activity of insulin given orally as nanocapsules. Humalog-loaded nanocapsules (50 IU/kg) were administered by gavage to streptozotocin-induced diabetic rats. Thirty minutes to 1 h after oral administration, significant levels of human insulin were detected in rat plasma. However, the concentrations were very heterogenous from one rat to another and no decrease of glycemia could be observed. In addition, parenteral injection of insulin in solution showed that high levels of the protein are necessary to decrease blood glucose concentration in diabetic rats. These concentrations were not reached after oral administration. The same dose of insulin decreased glycemia by 50% in normal rats and by only 25% in diabetics. This suggested that an insulino-resistance was developed by streptozotocin-induced diabetic rats.

Animals↗
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

pH compartmented w/o/w multiple emulsion: a diffusion study.

In order to develop w/o/w emulsions characterized by two separate aqueous phases of different pH, a preliminary study was carried out to obtain a better insight into the possible diffusion processes taking place between an inner acidic aqueous phase and an external phase of higher pH (pH approximately 6). In fact, such systems could be of great interest for pharmaceutical use. For this purpose, a model emulsion was formulated. The study of pH and conductivity showed that acidic species transport take place between the two aqueous compartments. The three main release mechanisms that might be responsible for this passage across the oil phase were investigated: breakdown of oil globules, facilitated transport by surfactant micelles across the oil phase or by Fickian diffusion. It appears that this last mechanism was involved. In order to control this diffusion process, an alkaline species, octadecylamine was introduced in the oil phase. This compound could form an ion pair with the lactate ion at the interface of the external aqueous phase and the oil phase, thus, limiting the acidification of the external aqueous phase.

Algorithms↗
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

Study of the breakup under shear of a new thermally reversible water-in-oil-in-water (W/O/W) multiple emulsion.

PURPOSE: Thickening of the external aqueous phase of W/O/W multiple emulsions is essential to increase the release under shear. However, it leads to globules bursting during fabrication. To reduce this problem, we have tested a novel thermally reversible hydrogel, EMP hydrogel. This way, the corresponding multiple emulsion (EMPME) would gel only at skin temperature, which may increase the active ingredient delivery when topically applied. METHODS: Samples were sheared at different shear rates and temperatures (20, 30, and 35 degrees C) with a controlled rheometer. A granulometric analysis was then performed with a laser diffraction granulometer, to assess the break up as a function of the shear rate at the three temperatures. Conductometric measurements (CDM 230 conductometer) provided the corresponding release curves. RESULTS: As we expected, EMPME exhibited a thermally reversible behavior. Compared to a reference emulsion thickened by carbopol, this new thermo-sensitive multiple emulsion displayed higher break up and fraction released at 35 degrees C. CONCLUSION: The first thermally reversible multiple emulsion has been developed in the present work. This one presents interesting advantages: (1) an easy fabrication process with a higher entrapment yield and (2) a higher fraction released at 35 degrees C compared with the reference emulsion.

Acrylic Resins↗
PubMed2000

Charcoal suspension for tumor labelling modifies macrophage activity in mice.

We have previously developed a charcoal suspension for injection into human breast cancers in order to facilitate their location during surgery. We observed that charcoal particles were ingested by intra and peritumoral macrophages, some of which carried the particles at some distance from the injection site. We studied the influence of the formulation parameters of the charcoal suspension for intratumoral injection on in vitro and in vivo activation and in vivo mobilization of mouse peritoneal macrophages after intra-peritoneal injection of 2 mL of each preparation. The influence of the charcoal origin (peat vs wood), granulometry, suspension vehicle (water for parenteral injection, vs saline), concentration and excipients were studied. Micronized peat charcoal in water for injection at the highest studied concentration reduced macrophage activation in vitro and in vivo. However, macrophage mobilization was weaker than after thioglycolate injection and did not seem to be charcoal dose-dependent. The additives incorporated in the charcoal suspension led in vivo to increased peritoneal macrophage activation and mobilization (mannitol, and glucose), only increased activation (polysorbate 80 and pluronic F68) or mobilization (dextran 40, egg lecithin, and cabosil), or inhibited both activation and mobilization (cremophor EL).

Animals↗
PubMed2000

Stability study of W/O/W viscosified multiple emulsions.

Stable multiple emulsions with a small proportion of primary emulsion containing different viscosifying agents in the outer aqueous phase were formulated. The multiple systems were assessed by evaluating several parameters, such as the macroscopic aspect, droplet size, release rate, and accelerated stability under elevated temperatures. The effect of different viscosifying agents at different concentrations on the stability and the multiplicity of the multiple emulsions was examined. The viscosity increased by increasing the concentration of the viscosifying agents. It also appeared that the viscosifying agents increased the temperature stability of the multiple emulsions. As a result, the formulation viscosified with Klucel was more stable, while the one prepared with carbomer viscosified the outer phase at much lower concentrations with much better skin feel.

Chemistry, Pharmaceutical↗
PubMed1999

W/O/W Multiple Emulsions Submitted to a Linear Shear Flow: Correlation between Fragmentation and Release.

The present work attempted to apply the theoretical framework described by Taylor to different multiple emulsions under shear. The results were in relatively good agreement with the theory. The correlation between the fragmentation and release studies was well proved. Moreover, these studies showed that mechanisms taking place during the breakup were complex and did not always lead to a total release of the entrapped electrolyte. Some phenomena such as a partial leakage of the internal aqueous compartment or the expulsion of aqueous microglobules covered by a residual lipophilic film were able to restrict the release. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Formulation of a charcoal suspension for intratumoral injection. Study of galenical excipients.

To tattoo human breast cancer prior to chemotherapy, radiotherapy, or surgery, thus allowing a better localization of the remaining tumor by the surgeon, we developed a formulation containing 10% charcoal suspended in water for parenteral preparations. The present study concerns a new step in the development of the charcoal suspension. We sought to determine whether the addition of various excipients could improve the formulation properties and affect the labeling of tumor by the suspension. We have tested surfactants (egg lecithin, polysorbate 80, Cremophor EL, and Pluronic F68), isotonisants (sugars such as glucose and mannitol), polysaccharides (dextrans 20 and 40), and Cabosil, a pyrogenated silica. Except for glucose and mannitol, which were added at a 5% concentration, the other excipients were added at a 0.1% concentration, they were dissolved in water for parenteral injection and sterilized at 120 degrees C for 20 min. We then measured diffusion in vivo in mammary tumor. In vivo, when injected intratumorally in mice, a greater diffusion of charcoal particles was noted within the tumor (in the case of egg lecithin, polysorbate 80, dextran 20 and 40, and glucose) and sometimes in some organs (e.g., Cremophor EL and mannitol). Pluronic F68 slightly improved the stability of the suspension and did not lead to marked diffusion at the injection site, but it showed slight toxicity and cannot be used in the formulation. We concluded that the best formulation was an aqueous 10% micronized peat charcoal suspension.

Adenocarcinoma↗
PubMed1998

Kinetics of swelling-breakdown of a W/O/W multiple emulsion: possible mechanisms for the lipophilic surfactant effect.

The properties and behavior of a W/O/W multiple emulsion formulation were analyzed during a swelling-breakdown process. Various experimental analyses, such as granulometry, rheology and conductimetry were performed, as well as a micropipette aspiration method. The predominant role of the lipophilic surfactant during the swelling phase confirmed. Two different mechanism can be proposed. Both imply the migration of the lipophilic surfactant from one interface to another and probably take place successively. The lipophilic surfactant could diffuse from the first to the second interface, thus rigidifying the membrane, or from the oily phase to the first interface, resulting in delayed coalescence of the aqueous droplets during swelling.

Emulsions↗
PubMed1997

Formulation of a charcoal suspension for intratumor injection. Part 1: Study of the nature, granulometry, and concentration.

PURPOSE: We developed a charcoal suspension formulation to be injected intratumorally so that human breast cancers can be tatooed prior to chemotherapy. This deposit is intended to guide the surgeon at the time of the biopsy and resection, especially when the tumor nodule is not visible. The stain should remain in the tumor as long as the patient is on chemotherapy and should be harmless. METHODS: We studied on the effect on the nature of the charcoal, its granulometric profile, and its concentration. We then measured diffusion in vitro, in gel, and in vivo in experimental tumors. RESULTS: The formulation selected was prepared with a peal charcoal suspension in water for parenteral injections, with 50% of the particles measuring on average between 2 and 5 microns. The finest particles (< 2 microns) seem to produce the greatest in vitro diffusion and are more readily phagocyted by macrophages and thus eliminated from the tumor by those cells. CONCLUSIONS: This charcoal suspension has satisfactory formulation characteristics and diffuses the least, be it in vitro or in vivo, mainly due to the granulometric distribution of the suspension.

Animals↗
PubMed1993

Multiple emulsions.

The purpose of this review is to update the information on multiple emulsions known to be promising delivery systems for both pharmaceuticals and cosmetic materials. The possibility of encapsulating active substances within liquid membranes may lead to interesting opportunities in both fields. Thus the formulation, manufacturing, stabilization, analysis and potential application of multiple emulsions seems to be worth surveying, putting a special emphasis on cosmetic applications.

Chemistry, Pharmaceutical↗