Biomedical subjects

J P Benoît

Publications and source records attributed to J P Benoît.

10 recordsLinked to original sources

PubMed2006

Formulation of sustained release nanoparticles loaded with a tripentone, a new anticancer agent.

The purpose of the present work is to develop nanoparticles of a new antitubulin agent of the family of tripentones by means of a phase inversion process. Dynamic light scattering, transmission electron microscopy and zeta-potential measurements were used to characterize tripentone loaded nanoparticles. From interfacial tension measurements and from the study of the rheological interfacial properties of the tripentone at the Labrafac-Solutol interface, the fraction of tripentone initially present in Labrafac would stay in the oily core of nanocapsules. Moreover, the interpenetration of some tripentone molecules within the surfactant units helps to the stabilization of the formulated nanoparticles. The encapsulation efficiency was determined by high performance liquid chromatography (HPLC) and was found to be above 95%. In vitro release studies were carried out in blank nanoparticles containing phosphate buffer, pH 7.4, at 37 degrees C. The drug release kinetics was measured by HPLC. Antiproliferative activity studies on L1210 cells showed that the cytotoxic activity of tripentone was totally recovered after encapsulation of the antitubulin agent in lipid nanoparticles. This study shows that lipid nanocapsules could be a promising and effective carrier for tripentone delivery in the treatment of cancers.

Animals↗

PubMed2005

Interactions between hen egg-white lysozyme, PEG2,000, and PLA50 at the air-water interface.

In this paper, we compared the efficiency of polymer films, made of a poly(ethylene glycol) (PEG2,000)/poly(d,l-lactide) (PLA50) mixture, or a PEG2,000-PLA50 copolymer, to prevent adsorption of a model protein, the hen egg-white lysozyme (HEWL), at the air-water interface. This was achieved by analyzing the surface pressure/surface area curves, and the X-ray reflectivity data of the polymer films spread on a Langmuir trough, obtained in absence or in presence of the protein. For both the mixture and the copolymer, the amount of protein adsorbed at the air-water interface decreases when the density of the polymer surface coverage increases. It was shown that even in a condensed state, the polymer film made by the mixture can not totally prevent HEWL molecules to adsorb and penetrate the polymer mixed film, but however, protein molecules would not be directly exposed to the more hydrophobic phase, i.e. the air phase. It was also shown that the configuration adopted by the copolymer at the interface in its condensed state would prevent adsorption of HEWL molecules for several hours; this would be due in particular to the presence of PEG segments in the interfacial film.

Adsorption↗

PubMed2003

Spectroscopic studies on poly(ethylene glycol)-lysozyme interactions.

In the present paper, different spectroscopic methods were applied to evaluate conformational changes of hen egg-white lysozyme (HEWL) in various solvents and in the presence of poly(ethylene glycol) (PEG). In citrate (0.007M, pH=6), or in Tris (0.1M, pH=7.4), no conformational change of the protein was measured across the range of concentrations tested. In addition, HEWL in ultra-pure water revealed no irreversible conformational change and no activity loss, at least at low concentrations (< or =0.2mg/ml). Whereas PEG can induce a reorganization of water molecules, no change of the secondary and tertiary protein conformations was observed in the presence of PEG. In addition, in the presence of PEG of various molecular weights, no change of enzymatic activity of the HEWL was observed across the range of concentrations tested.

Circular Dichroism↗

PubMed2003

Interfacial properties of adsorbed films made of a PEG2000 and PLA50 mixture or a copolymer at the dichloromethane-water interface.

Adsorption kinetics of films of poly(ethylene glycol) (PEG2000) studied by the dynamic pendant drop method showed that PEG2000 was more tensioactive at the dichloromethane (DCM)-water interface than at the air-water interface. When initially solubilized into DCM, PEG2000 segments would form an adsorbed layer with hydrophobic segments buried into the polymer chains turned toward the organic phase. Compression of this layer, accompanied by viscoelastic effects, led to expulsion of some hydrophilic tails toward the water phase. When initially dissolved in water, adsorption of PEG2000 segments led to an elastic PEG2000 layer organized on both sides of the interface. Results showed that when the PEG2000-PLA50 (poly(D,L-lactide)) copolymer film was adsorbed at the DCM-water interface, it resulted in a mixed layer exclusively turned toward DCM and its rheological properties were governed by PLA50. When adsorption at the DCM-water interface resulted from a physical mixture of PEG2000 and PLA50, rheological properties of the film were influenced by the initial localization of PEG2000 in the bulk phases. In the case of a mixed film formed by the adsorption of PLA50 from DCM and PEG2000 from water, results showed that PEG2000 segments totally pushed those of PLA50 away from the interface and exclusively influenced the behavior of the mixed film.

Kinetics↗

PubMed2002

Properties of polyethylene glycol 660 12-hydroxy stearate at a triglyceride/water interface.

This study proposed a method to understand the surfactant role in the first step of the formulation of a novel generation of lipidic nanocapsules. A dynamic rheological protocol was applied using a pendant drop tensiometer in order to determine the interfacial properties of the initial mixture implied in the first formulation step. The response, in terms of interfacial elasticities, described how this mixture led to monodisperse nanometer size range structures after a physico-chemical constraint.

Capsules↗

PubMed1996

Preparation, purification and morphology of polymeric nanoparticles as drug carriers.

The aim of this work was to prepare biodegradable poly(D,L-lactic acid-co-glycolic acid) copolymer (PLAGA) nanoparticles by the solvent evaporation process and to incorporate an antifungal antibiotic, amphotericin B. Blank nanoparticles obtained were 130 +/- 27 nm in diameter. When amphotericin B was added in the organic phase, the final suspension showed two populations due to unbound drug. Free amphotericin B was removed by contacting the nanoparticle suspension with an adsorbent polymer. Amberlite XAD16, and subsequently ultrafiltering the medium. The drug payload was between 0.7 and 1.3%. To gain more insight in the cause of this low loading, we studied progesterone-loaded nanoparticles using PLAGA and polystyrene as models because progesterone and these polymers exhibit a degree of miscibility. In the case of polystyrene, nanoparticle drug content reached 8%.

Amphotericin B↗

PubMed1994

End-chain radiolabeling and in vitro stability studies of radiolabeled poly(hydroxy acid) nanoparticles.

In order to study the tissue distribution of biodegradable nanoparticles after oral administration in animals, end-chain-radiolabeled poly(D,L-lactides) were prepared. Two groups of polymers (Mn = 7500, I = 2.4 and Mn = 28000, I = 1.4 as determined by organic size-exclusion chromatography) were chemically modified by reaction of [14C]acetic anhydride with hydroxyl end-chain groups. The activities of both resulting radioactive poly(D,L-lactides) varied from 57 to 1140 microCi/g. Poly(D,L-lactide) or poly(D,L-lactide-co-glycolide) nanoparticles containing various amounts of radioactive polymer were prepared according to the solvent evaporation process with acetone as cosolvent with methylene chloride in the organic phase. Their mean diameter was 133 +/- 25 nm, measured by photon correlation spectroscopy. The radiolabeled-end-group stability of these particles in buffer solutions was found to be greater when the matrix was made from the radiolabeled poly(D,L-lactide) having the highest molecular weight and the lowest polydispersity index. The polymer-chain stability was totally retained for at least 1 week in a phosphate buffer, pH 7.4, i.e. for the selected experiment time.

Carbon Radioisotopes↗

PubMed1990

Influence of average molecular weights of poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 on phase separation and in vitro drug release from microspheres.

The phase separation of fractionated poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 was determined by silicone oil addition. Polymer fractionation by preparative size exclusion chromatography afforded five different microsphere batches. Average molecular weight determined the existence, width, and displacement of the "stability window" inside the phase diagrams, and also microsphere characteristics such as core loading and amount released over 6 hr. Further, the gyration and hydrodynamic radii were measured by light scattering. It is concluded that the polymer-solvent affinity is largely modified by the variation of average molecular weights owing to different levels of solubility. The lower the average molecular weight is, the better methylene chloride serves as a solvent for the coating material. However, a paradoxical effect due to an increase in free carboxyl and hydroxyl groups is noticed for polymers of 18,130 and 31,030 SEC (size exclusion chromatography) Mw. For microencapsulation, polymers having an intermediate molecular weight (47,250) were the most appropriate in terms of core loading and release purposes.

Drug Compounding↗

PubMed1986

Formation and characterization of cisplatin loaded poly(d,l-lactide) microspheres for chemoembolization.

Cisplatin, a slightly water soluble anticancer drug, has been incorporated into biodegradable poly(d,l-lactide) microspheres using the solvent evaporation process. The optimal experimental conditions to produce spherical and separate drug-loaded particles (45% cisplatin) were as follows: the dispersing phase was a mixture of 0.05% methylcellulose and 4% polyvinyl alcohol (8 mPa-s grade); and the optimal poly(d,l-lactide) concentration in the organic phase was found to be greater than or equal to 7.16%. Microscopic studies showed that increasing the drug content in the microspheres produced the appearance of rod-like crystals at the microparticle surface. In addition, the cisplatin crystals were found homogeneously distributed in the polymer matrix, even at a high drug content. Increased viscosities of the organic phase enhanced the mean microsphere size, while increasing the emulsifier concentration in the aqueous phase decreased the average particle size. The drug incorporation efficiency was markedly improved after saturation of the dispersing phase with cisplatin. It was also noted that the amount of drug incorporated increased with increasing mean microsphere diameter. The methylene chloride content entrapped within the microspheres was found to depend upon the microsphere size distribution and the cisplatin content. An increase of the microsphere system porosity, by the addition of 10% cyclohexane in the organic phase, caused a reduction in the residual methylene chloride content. Finally, the in vitro release kinetics of cisplatin were influenced by the drug loading.

Chemistry, Pharmaceutical↗

PubMedDate not supplied

Biodegradable cross-linked albumin microcapsules for embolization.

The interfacial polymerization process used in the present study produced individual cross-linked albumin microcapsules, the particle size of which depended on the emulsification stirring rate. The variation in cross-linking agent concentration altered the microcapsule wall properties. As shown by SEM observations, microcapsules prepared with low acyl chloride concentrations presented rippled surfaces, while the surfaces of the microcapsules prepared with high acyl chloride concentrations were smooth. It was then suggested that the membranes of the weakly cross-linked microcapsules consisted of cross-linked and denatured albumin. Embolization experiments in the dog kidney showed that the weakly cross-linked microcapsules were biodegradable within 7 days, whereas the highly cross-linked microcapsules were degraded over more than 14 days and led to prolonged ischaemia. The results of the histological experiments carried out on a further eight dogs supported the previous findings yielded by the angiographical experiments. Moreover, they indicated that no foreign body reaction occurred. The lack of this inflammatory granuloma should be attributed to the rapid biodegradation of the microcapsules which produced reversible ischaemic lesions.

Animals↗