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Biomedical subjects

P Maincent

Publications and source records attributed to P Maincent.

At least 19 recordsLinked to original sources
PubMed2001

Bovine mastitis and intramammary drug delivery: review and perspectives.

Intramammary infections (IMIs) represent a major feature in bovine pathology. The treatment of IMIs concern antimicrobial substances. Therapeutic strategies involve administration of immediate release formulations during lactation with or without long-acting formulations during the dry period. Current treatments are not very successful and cure rates are poor, especially towards Staphylococcus aureus which is responsible for chronic infections and huge economic losses. New strategies have recently been investigated. These include particular immunomodulators like lysostaphin or cytokines, and novel formulations (e.g. liposomes, microparticles or nanoparticles) that allow uptake of the active component by phagocytes and thus prolong an enhanced antibacterial activity.

Animals↗
PubMed2001

Design of rolipram-loaded nanoparticles: comparison of two preparation methods.

The aim of the present work was to investigate the preparation of nanoparticles as a potential drug carrier and targeting system for the treatment of inflammatory bowel disease. Rolipram was chosen as the model drug to be incorporated within nanoparticles. Pressure homogenization-emulsification (PHE) with a microfluidizer or a modified spontaneous emulsification solvent diffusion method (SESD) were used in order to select the most appropriate preparation method. Poly(epsilon-caprolactone) has been used for all preparations. The drug loading has been optimized by varying the concentration of the drug and polymer in the organic phase, the surfactants (polyvinyl alcohol, sodium cholate) as well as the volume of the external aqueous phase. The rolipram encapsulation efficiency was high (>85%) with the PHE method in all cases, whereas with the SESD method encapsulation efficiencies were lower (<40%) when lower surfactant concentrations and reduced volume of aqueous phase were used. Release profiles were characterized by a substantial initial burst release with the PHE method (25-35%) as well as with the SESD method (70-90%). A more controlled release was obtained after 2 days of dissolution with the PHE method (70-90%), no further significant drug release was observed with the SESD method.

Algorithms↗
PubMed2001

Influence of the preparation method on the physicochemical properties of tolbutamide/cyclodextrin binary systems.

Tolbutamide (TBM) was found to form an inclusion complex with beta cyclodextrin (beta-CD) in solution and in solid state. Inclusion complex formation between tolbutamide and beta-cyclodextrin in aqueous solution was studied by phase solubility and spectral shift methods. The apparent stability constant Ks calculated by these techniques, in water, were estimated as 195.7 and 236.5 M(-1), respectively. The phase solubility studies revealed a B(S)-type diagram with an inclusion complex of 1:2 molar ratio. The solid inclusion complexes of TBM and beta-CD were prepared at a molar ratio of 1:2 by kneading, coprecipitation, freeze-drying, and spray-drying methods. In addition, the physical mixture was prepared. Characterization of TBM: beta-CD inclusion was performed using differential scanning calorimetry (DSC), Raman spectroscopy, and X-ray diffractometry and by application of a so-called ether wash method. All the inclusion systems investigated led to a significant improvement in the dissolution over free TBM, and the dissolution rate of the active material was observed to be independent of the preparation method.

Calorimetry, Differential Scanning↗
PubMed2001

Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease.

The use of nanoparticles for targeted oral drug delivery to the inflamed gut tissue in inflammatory bowel disease was examined. Such a strategy of local drug delivery would be a distinct improvement compared with existing colon delivery devices for this disease. An experimental colitis was induced by trinitrobenzenesulfonic acid to male Wistar rats. Rolipram, an anti-inflammatory model drug, was incorporated within poly(lactic-coglycolic acid) nanoparticles, which were administered once a day orally for five consecutive days. A clinical activity score and myeloperoxidase activity were determined to assess the inflammation, whereas an adverse effect index reflected the remaining neurotropic effect of rolipram resulting from its systemic absorption. All nanoparticle formulations proved to be as efficient as the drug in solution in mitigating the experimental colitis. The clinical activity score and myeloperoxidase activity decreased significantly after the oral administration of rolipram nanoparticles or solution. During the next 5 days when animals were kept without drug treatment the drug solution group displayed a strong relapse, whereas the nanoparticle groups continued to show reduced inflammation levels. The rolipram solution group had a high adverse effect index, whereas the rolipram nanoparticle groups proved their potential to retain the drug from systemic absorption as evidenced by a significantly reduced index. This new delivery system enabled the drug to accumulate in the inflamed tissue with higher efficiency than when given as solution. The nanoparticle deposition in the inflamed tissue should be given particular consideration in the design of new carrier systems for the treatment of inflammatory bowel disease.

Animals↗
PubMed2000

The preparation and evaluation of poly(epsilon-caprolactone) microparticles containing both a lipophilic and a hydrophilic drug.

An original dosage form for oral delivery based on the encapsulation of both, lipophilic and hydrophilic drugs, in poly(epsilon-caprolactone) (PCL) microparticles prepared either by the oil-in-water (o/w) or the water-in-oil-in-water (w/o/w) solvent evaporation method was developed. Microparticles were characterized in terms of morphology, size, encapsulation efficiency and drug release. The physical state of the drugs and the polymer was determined by scanning electron microscopy (SEM), X-ray powder diffractometry, and differential scanning calorimetry (DSC). Nifedipine (calcium antagonist) and propranolol HCl (beta-blocker), used for the treatment of hypertension, were chosen as lipophilic and hydrophilic drugs. The microparticles were spherical with diameters in the range of 191-351 microm by the o/w-method, and in the range of 302-477 microm by the w/o/w-method. The encapsulation efficiency (EE) was 91% for nifedipine and 37% for propranolol HCl with the o/w-method, and 83% for nifedipine and 57% for propranolol HCl with the w/o/w-method. DSC and X-ray diffraction studies showed that PCL maintained its semi-crystalline structure, while the drugs were either dispersed or dissolved in the polymer. In vitro release studies revealed a controlled release of nifedipine and propranolol HCl from microparticles prepared by the o/w-method; a burst release of propranolol HCl was observed from microparticles prepared by the w/o/w-method. In conclusion, microparticles containing both a hydrophilic and a lipophilic drug were successfully prepared.

Adrenergic beta-Antagonists↗
PubMed2000

Influences of process parameters on nanoparticle preparation performed by a double emulsion pressure homogenization technique.

The preparation of nanoparticles (NP) as an improved colloidal carrier system for proteins was investigated. Bovine serum albumin (BSA) was used as model drug. Owing to the high solubility of the protein in water, the double emulsion technique has been chosen as one of the most appropriate method. In order to both reaching submicron size as well as increasing the grade of monodispersity compared to previous preparation techniques, a microfluidizer as homogenization device was used. All experiments were performed using two biodegradable polymers, poly[D,L-lactic-co-glycolic acid] 50/50 (PLGA) and poly[epsilon-caprolactone] (PCL). The homogenization procedure has been optimized with regard to particle size and monodispersity by studying the influence of the homogenization time as well as the amount of polymer and surfactant in the external aqueous phase. The drug loading has been improved by varying the concentration of the protein in the inner aqueous phase. By increasing the protein concentration in the inner aqueous phase the polydispersity was slightly higher, while the particle size was not influenced significantly. The BSA encapsulation efficiency decreased with higher protein concentration in the inner aqueous phase. All release profiles were characterized by a initial burst effect, a higher release rate was obtained after 4 weeks for PLGA NP (60%) compared with PCL NP (47%).

Animals↗
PubMed2000

Physicomechanical properties of biodegradable poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) films in the dry and wet states.

The objective of this study was to investigate the mechanical properties (% elongation and puncture strength) of poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) films as a function of exposure time to an aqueous medium and to correlate the mechanical properties to the degradation/erosion of the polymer as a function of the type of polymer [PLA, weight-average molecular weight (M(W)) 270,300, or PLGA 50:50, M(W) 56,500], the type of plasticizer [(triethyl citrate (TEC) or acetyltributyl citrate (ATBC)], and the exposure time to pH 7.4 phosphate buffer. The glass transition temperature of the films was measured by differential scanning calorimetry (DSC), the molecular weight by size exclusion chromatography (SEC), and the polymer erosion and hydration gravimetrically. The mechanical properties were strongly affected by the type of polymer and plasticizer. PLGA films showed a faster loss of mechanical integrity. TEC, the water-soluble plasticizer, leached from the films, resulting in major differences in the mechanical properties (flexibility) when compared with films plasticized with the more permanent, water-insoluble ATBC. A significant difference in M(W) decrease was seen between plasticizer-free and plasticizer-containing PLA films, but not for PLGA films. Plasticized PLA films, which were above their glass transition temperature in the rubbery state, showed a faster decrease in M(W) than plasticizer-free PLA ones, which were in the glassy state. The plasticizer addition to the lower M(W) PLGA did not enhance the polymer degradation; the plasticizer-free PLGA was already in the rubbery state. Major differences between the two polymers were also seen in the mass loss and the water uptake studies. After 4 weeks, the mass loss was between 2.6 and 7.0% and the water uptake between 10.1 and 21.1% for PLA films, whereas for PLGA films, the mass loss was between 40.3 and 51.3% and the water uptake between 221.9 and 350.6%. 2000 Wiley-Liss, Inc.

Biocompatible Materials↗
PubMed2000

[Ways to improve ocular bioavailability for topical applications].

The anatomical, physiological and pharmacological properties of the eye explain the short pre-corneal residence time and the poor bioavailability of most eye-drop solutions. Many approaches have been proposed to increase ocular bioavailability of drugs. Most eye-drops include a viscosity agent in their formulation to significantly prolong residence time although the increased viscosity is limited due to patient discomfort. More recent developments include biodegradable inserts, eye-drop based on cyclodextrins, liposomes or nanoparticles.

Biological Availability↗
PubMed1999

Biodegradable monodispersed nanoparticles prepared by pressure homogenization-emulsification.

The aim of the present work was to investigate the preparation of nanoparticles (NP) as potential drug carriers for proteins. The hydrophilic protein bovine serum albumin (BSA) was chosen as the model drug to be incorporated within NP. Owing to the high solubility of the protein in water, the double emulsion technique has been chosen as one of the most appropriate method. In order to reach submicron size we used a microfluidizer as a homogenization device with a view to obtaining NP with a very high grade of monodispersity. Two different biodegradable polymers, poly[D, L-lactic-co-glycolic acid] 50/50 (PLGA) and poly[epsilon-caprolactone] (PCL) has been used for the preparation of the NP. The drug loading has been optimized by varying the concentration of the protein in the inner aqueous phase, the polymer in the organic phase, the surfactant in the external aqueous phase, as well as the volume of the external aqueous phase. The BSA encapsulation efficiency was high (>80%) and release profiles were characterized by a substantial initial burst release for both PLGA and PCL NP. A higher release was obtained at the end of the dissolution study for PLGA NP (92%) compared with PCL NP (72%).

Biocompatible Materials↗
PubMed1999

Evaluation of peroral silicone dosage forms in humans by gamma-scintigraphy.

Gastric emptying of oral silicone dosage forms was studied in humans by gamma-scintigraphy. To achieve a constant and predictable residence time in the stomach, three different formulations based on known concepts such as controlled swelling were investigated. The importance of physical parameters such as size or shape were also examined to assess the feasibility of designing a dosage form for gastric retention. Three shapes: minimatrices, extruded rods and moulded slabs were screened. To label the silicone polymer, two isotopes, used routinely in nuclear medicine departments, were selected: iodine-123 and indium-111. To select the most suitable isotope, the yield and the stability of the labelling were determined in vitro on the pharmaceutical dosage forms. The residence time of these silicone formulations, labelled with iodine and administered in hard gelatine capsules, was monitored in 12 subjects with a gamma camera. The study was performed under fed conditions after ingestion of a standardised meal labelled with indium. The minimatrices provided at least 3 h retention, slabs exhibited 4 h 40 min retention. For the rods the mean residence time in the stomach was around 4 h 20 min. In addition, a correlation was established between the gastric emptying of rods and the half-gastric residence time of meal. On the contrary, such a correlation was not observed for the slabs.

Administration, Oral↗
PubMed1999

Effect of the formulation on the in-vitro release of propranolol from gellan beads.

Gellan gum beads of propranolol hydrochloride, a hydrophilic model drug, were prepared by solubilising the drug in a dispersion of gellan gum and then dropping the dispersion into calcium chloride solution. The droplets formed gelled beads instantaneously by ionotropic gelation. Major formulation and process variables which might influence the preparation of the beads and the drug release from gellan gum beads were studied. Very high entrapment efficiencies were obtained (92%) after modifying the pH of both the gellan gum dispersion and the calcium chloride solution. The beads could be stored for 3 weeks in a wet or dried state without modification of the drug release. Oven-dried beads released the drug somewhat more slowly than the wet or freeze-dried beads. The drug release from oven-dried beads was slightly affected by the pH of the dissolution medium. Gellan gum could be a useful carrier for the encapsulation of fragile drugs and provides new opportunities in the field of bioencapsulation.

Calcium Chloride↗
PubMed1999

Comparison of the biodistribution in mice of 111indium oxine encapsulated into poly(lactic-co-glycolic)-D,L-85/15 and poly(epsilon caprolactone) nanocapsules.

Poly(lactic-co-glycolic)-D,L-85/15 (PLAGA) nanocapsules and poly(epsilon caprolactone) (PCL) nanocapsules were labeled with a relatively long half-life compound that is usually used in humans; that is, 111In-labelled oxine (111In oxine). This labeling technique led to a high 111In oxine entrapment efficiency and good stability during dialysis against phosphate buffer and phosphate buffered albumin solution. Because of these characteristics, the nanocapsules biodistribution was followed up after intravenous administration for up to 96 h by determining the gamma activity in the tissues after sampling. The administration of the PCL-encapsulated 111In oxine led to a decrease in the blood radioactivity and an increase in the liver radioactivity compared with the solution. This effect was even more pronounced with the PLAGA nanocapsules. Finally, the activity level in other tissues, such as the kidneys, the lungs, and the spleen, appeared to be rather low and only slightly affected by the encapsulation into one or the other polymer.

Animals↗
PubMed1998

Microporous microparticles designed as stable immunoadsorbents.

We have developed a solid-phase immunoadsorbent based on encapsulated goat anti-apolipoprotein B polyclonal antibodies previously crosslinked with a 0.25% glutaraldehyde solution, and designed to remove by immunoaffinity the excess of apolipoproteins B from the plasma of patients affected by familial hypercholesterolemia. Compared to a classical immunoadsorbent prepared by activation of Sepharose CL-4B with cyanogen bromide, the resulting immunoadsorbent exhibits both optimal adsorption capacity and stability over the entire range of chemical and biochemical conditions during its practical handling. This approach will serve as a model system to demonstrate the applicability of microparticles as immunoadsorbents, which can be achieved for other encapsulated crosslinked proteins.

Adsorption↗
PubMed1998

Influence of different physicochemical conditions on the release of indium oxine from nanocapsules.

The main purpose of this study was to determine the influence of factors (pH, enzymes, etc.) chosen partially to mimic in vivo conditions on the release of a model drug, indium oxine, from polyepsiloncaprolactone (PCL) nanocapsules in vitro. A nanocapsule suspension, an emulsion (O/W), and a solution in olive oil were prepared in order to compare the release of a radioactive tracer, indium oxine, as a function of time by an in vitro dialysis method. Nanocapsules were prepared by interfacial deposition of PCL and characterized by particle size distribution (laser light scattering) and determination of the polymer molecular weight by gel permeation chromatography (GPC). The results of this study suggest that the partition coefficient between the acceptor medium and the olive oil is the major parameter governing the release of the isotope, at least in the absence of significant enzyme activity. The PCL wall of nanocapsules is a barrier that does not seem to retard the release of indium. The addition of porcine liver esterases accelerated the degradation of PCL. This study confirms that the release of a drug from nanocapsules may be very different depending on the in vivo location, that is, the administration site.

Dosage Forms↗
PubMed1998

Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method.

Nanoparticles were prepared by the double emulsion method (w/o/w), using methylene chloride as an organic solvent and polyvinyl alcohol (PVA) or human serum albumin (HSA) as a surfactant. Experimental parameters such as the preparation temperature, the solvent evaporation methods, the internal aqueous phase volume, the surfactant concentration and the polymer molecular weight were investigated for particle size, the zeta potential, the residual surfactant percentage and the polydispersity index. Preparation parameters leading to particles with well-defined characteristics such as an average size around 200 nm and a polydispersity index lower than 0.1 were identified. The conditions were optimized to ensure protein encapsulation: a cool temperature, a short processing time, a sufficient internal aqueous phase and careful washing. It appeared that the higher the surfactant concentration in the external aqueous phase was, the smaller the particles, the lower the polydispersity index and the higher the residual amount of surfactant were. For PVA or HSA, the agreement between the convenient surfactant concentration and its critical aggregation concentration could be emphasized. Otherwise, an increased polymer molecular weight led both to a slightly decreased particle size and to a lower polydispersity index. Moreover, multilayer absorption of PVA which does not depend on Poly(lactic-acid) molecular weight was exhibited. Finally, the zeta potential resulted from the polymer molecular weight and the residual PVA.

Drug Delivery Systems↗
PubMed1998

Preparation and characterization of nanoparticles containing an antihypertensive agent.

Isradipine, an antihypertensive agent, was encapsulated by the nanoprecipitation method using polymers including poly(epsilon-caprolactone), poly(D,L-lactide) and poly(d, L-lactide-co-glycolide). In vitro scanning electron microscopy and differential scanning calorimetry were used to characterize the nanoparticles. The average diameters of the nanoparticles ranged from 110 nm to 208 nm. PCL nanoparticles were larger than nanoparticles prepared with the other polymers. The zeta potential of the nanoparticles was negative, with values of about -25 mV which promoted good stabilization of the particles. The amorphous state of PLA and PLAGA non-loaded nanoparticles and the semi-crystalline state of PCL were demonstrated with X-ray diffraction and differential scanning calorimetry. For all nanoparticles, isradipine was found to be totally amorphous in the polymer which suggested that the drug was molecularly dispersed in the matrix. The colloidal suspensions displayed a sustained release profile in comparison with the drug release profile of isradipine in a PEG solution. Results from this investigation suggest that these nanospheres will be a good candidate delivery system for oral administration, to reduce the initial hypotensive peak and to prolong the antihypertensive effect of the drug.

Antihypertensive Agents↗
PubMed1998

Determination of heparin in aqueous solutions.

OBJECTIVE: To develop a volumetric method for assaying heparin in aqueous media. METHOD: Heparin is precipitated out with an aqueous solution of an organic amine by titration and the end-point is based on the measurement of the medium dielectric permittivity. We studied the titration of a 500 IU/ml heparin solution with a 0.08 M cetylpyridinium chloride solution at pH 6.8. Then, we assayed sulphate groups selectively at pH 2. The results were compared against a classical method of SO2 determination. The sensitivity and reproducibility of the volumetric method were evaluated at pH 6.8 and compared with the characteristics of a chromogenic method, usually used for the assay of heparin in biological fluids. RESULTS: A linear relationship between anticoagulant activity and sulphate and carboxyl group concentration was observed. The method was less sensitive but more reproducible than the chromogenic method. CONCLUSION: The proposed method can be used for aqueous solutions and is easy to carry out. It can be fully automated and applied to formulation studies.

Cetylpyridinium↗