Search PubMed⌕ Search

Biomedical subjects

J P Benoit

Publications and source records attributed to J P Benoit.

At least 73 records · Page 4Linked to original sources
PubMed1989

Doxorubicin-loaded nanoparticles: increased efficiency in murine hepatic metastases.

Free doxorubicin and doxorubicin associated with polyisohexlycyanoacrylate were tested for their therapeutic efficiency in hepatic metastasis-bearing mice. The metastases originated from the M 5076 reticulum cell sarcoma. Irrespective of the dose and the administration schedule, the reduction of the number of metastases was much larger with the doxorubicin-loaded nanoparticles than with free doxorubicin. This was clearly confirmed by histological examination. Although pharmacological and pharmacokinetic data indicated a strong capture of the nanoparticles by the hepatic issue, the mechanism of nanoparticle therapeutic efficiency remains unclear.

Animals↗
PubMed1989

In-vitro evaluation of filaricidal activity of GABA and 1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl: a diglyceride prodrug.

A diglyceride ester of gamma-aminobutyric acid (GABA) has been synthesized and its filaricidal activity compared with GABA, and progabide in-vitro, on infective larvae and microfilariae of Molinema dessetae, a rodent filaria. GABA induced paralysis in infective larvae but was inactive on microfilariae. There were interactions between the culture medium and GABA. The ester drug at 0.1 mmol L-1 (1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl) was as active as progabide on infective larvae and hundredfold more potent than GABA. Its microfilaricidal activity at 1 mmol L-1 was lower than that progabide at 0.1 mmol L-1 but a delayed effect was observed. The data confirm filariae sensitivity to GABA derivatives.

Animals↗
PubMed1988

Magnetically responsive microspheres for the pulsed delivery of insulin.

This paper describes a new formulation for triggered delivery of insulin which consisted of magnetic particles dispersed in alginate spheres. When magnetic field was applied to that system, the release rate of insulin was about 50 times higher than in the absence of magnetic field. The influence of oscillating magnetic field was tested, in the same experimental conditions, on polyethylenimine cross-linked alginate spheres. In that case, the pulsed delivery of insulin occurred not immediately but during the period just after applying the magnetic field. The proposed magnetically responsive alginate spheres open new perspectives for the rhythmically delivery of peptides.

Alginates↗
PubMed1987

Binding mechanism of doxorubicin in ion-exchange albumin microcapsules.

The absorption efficiency of cross-linked albumin microcapsules was evaluated as a function of various experimental conditions in an attempt to elucidate the doxorubicin binding mechanism of these microcapsules. The amount of drug absorbed augmented with increasing doxorubicin concentration until saturation was reached. Neither a Langmuir nor a Freundlich isotherm relationship was observed, indicating that the fixation of doxorubicin on the microcapsule walls did not follow a common physical adsorption process. Decreasing the mean particle diameter of the microcapsules increased the absorption rate and the total amount of doxorubicin absorbed, as expected. The absorption rate was enhanced by the elevation of the stirring rate of the aqueous drug solution. Furthermore, the presence of electrolytes in this aqueous solution profoundly altered the absorption profile of doxorubicin. Increasing the NaCl concentration in the solution reduced the total amount of drug absorbed. Moreover, the nature of the cation used also affected the absorption profile. These results suggested that there is a competitive fixation of the cation on the binding sites (identified as R-COO groups) available to the drug molecules. The weakly cross-linked microcapsules acted as cation-exchange resins which can exchange their labile sodium with the protonated drug present in the solution. This was also confirmed by the results of the titrimetric assay of the acidic microcapsules with NaOH.

Absorption↗
PubMed1987

Calcium and thiocyanate interactions with crosslinked albumin microcapsules: influence of the reticulation rate.

Ca2+ and SCN- interactions with strongly or lightly crosslinked albumin microcapsules were studied, using 45Ca2+ for a pH range varying from 5.5 to 7.8 and 14SCN- ions for the range 2.15 to 3.0. With strongly crosslinked albumin, the Scatchard plots of equilibrium isotherms indicate a maximum number of binding sites for Ca2+ ions, when N is equal to 12 and an apparent association constant, K' is equal to 7.8 X 10(3) l/mol. For the weakly crosslinked albumin, this constant is equal to 11 X 10(3) l/mol and the variation of calcium absorption with pH has an unusual shape, with a maximum at pH 6.5. The measurement of SCN- ion absorption by lightly crosslinked microcapsules indicates a K' value of 5.4 X 10(3) l/mol and an N value of 7 for pH 2.15. These values are, respectively, 8.3 X 10(3) l/mol and 2 for pH 2.15 when using strongly crosslinked microcapsules.

Absorption↗
PubMed1987

[Experimental study on osteosarcoma of local chemotherapy diffusing from surgical acrylic cement and plaster].

An experimental study has been made to explore the possibility of using plaster or surgical cement as a vehicle for the diffusion of local chemotherapeutic agents in osteosarcoma. In vitro, leeching out of methotrexate from plaster or acrylic cement occurred with a peak during the first few hours followed by a decreasing curve lasting for an average of two weeks. In dogs suffering from a spontaneous osteosarcoma, the loss of substance produced by excision was filled with cement to which methotrexate had been added extemporaneously. This method of administration produced a general diffusion of methotrexate whose blood levels were measured for three to five days. In laboratory rats into which osteosarcomata had been grafted, tablets of plaster containing antimitotic drug were implanted into the tumour, which was left in situ. This made it possible to show that the local chemotherapy was having a true effect, particularly when the antimitotic used was cisplatinum. In patients who had acrylic cement containing methotrexate inserted during operation, local diffusion resulted in very high concentrations, evidenced by the concentration found in fluid obtained from suction drains during the early days after operation.

Animals↗
PubMed1986

5-Fluorouracil:carnauba wax microspheres for chemoembolization: an in vitro evaluation.

5-Fluorouracil:carnauba wax microspheres were prepared using a meltable dispersion process with the aid of a surfactant as a wetting agent. It was noted that only hydrophilic surfactants were able to wet the 5-fluorouracil and substantially increased its content in the microspheres. No marked effect was observed in the particle size distribution of the solid microspheres as a function of the nature of the surfactant. Increasing the stirring rate in the preparation process decreased, first, the mean droplet size of the emulsified melted dispersion in the vehicle during the heating process, and, consequently, the mean particle size of the solidified microspheres during the cooling process. 5-Fluorouracil cumulative release from the microspheres followed first-order kinetics, as shown by nonlinear regression analysis. Although the kinetic results were not indicative of the true release mechanism from a single microsphere, it was believed that 5-fluorouracil release from the microspheres was probably governed by a dissolution process, rather than by a leaching process through the carnauba wax microspheres.

Fluorouracil↗
PubMed1986

The formation and characterization of hydrocortisone-loaded poly((+/-)-lactide) microspheres.

The solvent evaporation process has been used to form hydrocortisone-loaded microspheres from poly((+/-)-lactide) (PLA) and a lactide-glycolide copolymer (65/35). Methylene chloride was the casting solvent. Partially hydrolysed (88%) poly(vinyl alcohol) and methylcellulose were used as aqueous phase emulsifiers. Methylcellulose was preferred, because it gave stable emulsions as the amount of hydrocortisone being encapsulated increased whereas poly(vinyl alcohol) did not. With methylcellulose as the emulsifier, a broad size range of spherical microspheres containing up to 50% (w/w) hydrocortisone could be prepared. Thermal and X-ray analyses established that poly((+/-)-lactide) microspheres containing hydrocortisone retained thermal events characteristic of both materials. This is evidence that such microspheres contain, to some extent, crystalline hydrocortisone domains dispersed in a PLA matrix. But most of the encapsulated drug was molecularly dispersed in the PLA glass. The stability of hydrocortisone in microspheres was evaluated in different storage conditions: no degradation of drug was found. The release of hydrocortisone from 250-350 microns diameter microspheres into agitated 37 degrees C water (nitrogen atmosphere) was determined by HPLC analysis. The microspheres evaluated had initial hydrocortisone payloads of 12 to 47% (w/w). The rate of drug release increased as the initial drug payload carried by the microspheres increased. The release data are not adequately described by zero order, first order, or square-root-of-time release kinetics. Drug release from microspheres that contain 12% (w/w) hydrocortisone approached a plateau value well below the amount of drug actually carried by the microspheres. This is particularly true for hydrocortisone encapsulated in lactide-glycolide polymer.

Calorimetry, Differential Scanning↗
PubMed1984

Characterization of drug-loaded poly(d,l-lactide) microspheres.

Lomustine and progesterone have been incorporated in biodegradable poly(d,l-lactide) microspheres by evaporating dichloromethane from stirred dichloromethane-in-water emulsions. Spherical microspheres with lomustine or progesterone payloads less than or equal to 23% were obtained. Higher lomustine payloads gave irregularly shaped particles. Microspheres with less than or equal to 68% progesterone were obtained, but free drug crystals formed on the surface of such microspheres. Increased agitation rates decreased mean microsphere size. Addition of drug to the dichloromethane phase increased average particle size relative to that obtained with drug-free microspheres prepared under the same experimental conditions. Complete evaporation of the dichloromethane, while the medium was continuously stirred, promoted formation of free drug crystals in the aqueous phase. Increased emulsifier concentrations did not significantly enhance drug incorporation efficiency within the microspheres. Shelf-life stability of lomustine and progesterone was reduced by incorporation in the microspheres, presumably due to their molecular dispersion in the poly(d,l-lactide).

Crystallization↗