Biomedical subjects

D Duchêne

Publications and source records attributed to D Duchêne.

At least 19 recordsLinked to original sources

PubMed2002

In vitro inhibition of bovine herpes virus 1 reproduction with native and microencapsulated proteinase inhibitor aprotinin.

This study evaluated the antiviral effect of various dosage forms of proteinase inhibitor-aprotinin as a potential remedy for prophylactics and therapy of infectious bovine rhinotracheitis. Formulations of the inhibitor were tested for their influence on bovine herpes virus reproduction in cell cultures. Starch/bovine serum albumin microcapsules with aprotinin were prepared using interfacial cross-linking with terephthaloyl chloride and characterized for their morphology, size and release of the inhibitor. Two types of these microcapsules-impregnated and loaded with the inhibitor-were used in virus infectious studies. Native aprotinin possessed palpable dose-dependent antiviral effect inhibiting the virus reproduction up to 4.0 lg (10000-fold) and delaying the cytopathic effect up to 96 h in the concentration 800-3300 TIU/ml. The bioadhesive, biodegradable aprotinin-loaded microcapsules were the most effective antiviral drug as this formulation allowed to decrease virus infectious titer up to 4.0 lg and a delay in the cytopathic effect of up to 144 h in lesser doses of inhibitor compared with the native form. In comparison the antiviral effect of microcapsules impregnated with aprotinin was not so appreciable. It was interesting to note that the results of the experiments on diverse cultures were very similar. This was because the drugs influenced the fundamental processes of virus replication cycle.

Animals↗

PubMed2001

Combined hydroxypropyl-beta-cyclodextrin and poly(alkylcyanoacrylate) nanoparticles intended for oral administration of saquinavir.

The aim of this study was to prepare and characterize an hydroxypropyl-beta-cyclodextrin-saquinavir inclusion complex with the purpose of incorporating this complex into poly(alkylcyanoacrylate) nanoparticles in order to increase the drug loading. Hydroxypropyl-beta-cyclodextrin-saquinavir complex was characterized by thermal (differential scanning calorimetry), crystallographic (X-ray diffractography) and spectroscopic methods (circular dichroism, H1-NMR). Nanoparticles were prepared by polymerization of alkylcyanoacrylate monomers (isobutyl- and isohexylcyanoacrylate) in a water solution of the complex and further characterized. The apparent solubility of saquinavir was increased 400-fold at pH 7.0 in presence of hydroxypropyl-beta-cyclodextrin owing to the formation of a drug-cyclodextrin complex as demonstrated mainly by 1H NMR and confirmed by other techniques. Saquinavir-loaded nanoparticles could be easily prepared in the presence of a drug-cyclodextrin complex. It was found that large amounts of cyclodextrins remained associated with the particles, resulting in a 20-fold increase in saquinavir loading compared to nanoparticles prepared in the absence of cyclodextrins. This study has shown that the loading in saquinavir of poly(alkylcyanoacrylate) nanospheres could be dramatically improved by simultaneously increasing the apparent solubility of the drug in the preparation medium and the amount of cyclodextrin associated with the particles, making these nanospheres a promising system for oral application.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2001

Covalent coupling of asparagus pea and tomato lectins to poly(lactide) microspheres.

Lectin-poly(lactide) microsphere conjugates specifically designed for oral administration were prepared and their activity and specificity in presence of mucus were characterized. The presence of hydroxyl or amino groups suitable for covalent coupling of lectins by the glutaraldehyde method at the surface of the microspheres have been ensured by preparing the particles in presence either of poly(vinyl alcohol) (PVA) or bovine serum albumin (BSA). Tomato and asparagus pea lectins could be covalently attached to these particles (1.0-1.3 mg/m(2) of particles). The conjugates demonstrated a 4-10 fold increase in their interactions with mucus compared to control particles. Moreover, the sugar specificity of the lectins was maintained.

Glutaral↗

PubMed2001

Gastrointestinal transit and mucoadhesion of colloidal suspensions of Lycopersicon esculentum L. and Lotus tetragonolobus lectin-PLA microsphere conjugates in rats.

PURPOSE: To investigate in vivo the fate and the behavior of lectin-particle conjugates after oral administration. METHODS: Two plant lectins were selected, namely Lycopersicon esculentum L. and Lotus tetragonolobus lectins, which have been reported to be specific for oligomers of N-acetyl-D-glucosamine and L-fucose, respectively, and conjugated to small poly(lactide) microspheres. Their intestinal transit was investigated in detail using radiolabeled particles. The transport and the distribution of the particles along the intestine, as well as their interactions with the intestinal mucosa, were determined after oral administration in rat. RESULTS: The overall transit of the particles was shown to be strongly delayed when the microspheres were conjugated to the lectins, mainly due to the gastric retention of the particles. A significant fraction of the conjugates adhered to the gastric and intestinal mucosae. No significant differences were observed after a preliminary incubation of lectin-microsphere conjugates with specific sugars. CONCLUSION: Although specific interactions could not be excluded, especially in the stomach, it was likely that adhesion was predominantly due to nonspecific interactions. These results could be attributed both to unfavorable physicochemical characteristics of the conjugates and to premature adsorption of soluble mucin glycoproteins, preventing any further specific adhesion.

Adhesives↗

PubMed2001

[Use of cyclodextrins in the formulation of polyalkylcyanoacrylate nanoparticles charged with different active ingredients].

Cyclodextrins were used to improve the loading capacity of biodegradable pol(yisobutyl cyanoacrylat)e nanoparticles, which were obtained by anionic polymerization in aqueous medium. We investigated the feasibility of blank nanoparticles in the presence of a series of cyclodextrins (5 mg/ml) and poloxamer 188 (1%). The smaller particles (87 +/- 3 to 103 +/- 6 nm) were obtained in the presence of hydroxypropyl beta- or gamma-cyclodextrin. The nanoparticle loading capacity investigated in the presence of hydroxypropyl beta-cyclodextrin, in the previous conditions, on a series of steroids revealed an increase varying from 5.5 times (megestrol acetate) to 130 times (prednisolone). Differential scanning calorimetry study of the active ingredient (progesterone) in the nanoparticles, revealed an amorphous or molecular state. The in vitro release of the active ingredient occurred very rapidly but reached a plateau depending on the nanoparticle size and the dissolution medium nature. All the active ingredient was released in the presence of esterases. The addition of a preformed hydroxypropyl beta-cyclodextrin/saquinavir inclusion compound to the preparation medium of poly(isobutyl [or] isohexyl cyanoacrylate) nanoparticles, resulted in a 20-fold increase in the encapsulation yield. Presently, poly(isobutyl cyanoacrylate) hydroxypropyl beta-cyclodextrin combined nanoparticles loaded with doxorubicin are in phase II clinical trials.

Cyanoacrylates↗

PubMed2000

Phase behavior of fully hydrated DMPC-amphiphilic cyclodextrin systems.

With the aim of exploring relationships between the chemical structure and the physico-chemical properties of amphiphilic beta-cyclodextrin, a reappraisal of the obtaining of pure heptakis (2,3-di-O-hexanoyl)-beta-cyclodextrin (beta-CDC(6)) was undertaken. In this paper the chemical characterization of the newly synthesized beta-CDC(6) and its ability to form mixed structures with dimyristoylphosphatidylcholine (DMPC) are reported. Miscibility of the two amphiphiles is examined: (i) in monolayers formed at the air-water interface by analyzing the surface pressure-area isotherms; and (ii) in fully hydrated mixtures by differential scanning calorimetry (DSC) and X-ray diffraction at small and wide angles. Results demonstrate that the beta-cyclodextrin derivative is partially miscible to the phospholipid: intimate mixing occurs at beta-CDC(6) molar ratios smaller than 7-15 mol%, depending on the dimensional scale considered, while beyond these compositions phase separation is observed. At the air-water interface, the miscibility region of the two compounds shows non-ideal behavior characterized by the non-additivity of the molecular areas in the mixed monolayers. At the three-dimension level, the formation of a beta-CDC(6)/DMPC mixed lamellar phase occurs except at beta-CDC(6) molar ratios close to 5 mol% at which a highly ordered structure is depicted below the solid-to-liquid state transition of the DMPC hydrocarbon chains. At beta-CDC(6) contents higher than 7 mol%, the mixed assemblies coexist with excess amphiphilic cyclodextrin which then forms a separated hexagonal structure.

Calorimetry, Differential Scanning↗

PubMed2000

Bioadhesive potential of gliadin nanoparticulate systems.

The objective of this work was to prepare, characterise and evaluate the adhesive potential of gliadin nanoparticulate carriers. Firstly, lectin-nanoparticle conjugates were obtained by the carbodiimide (CDI) covalent binding of Dolichos biflorus lectin (DBA) to the surface of gliadin nanoparticles (NP) containing carbazole (as a model lipophilic drug). The DBA binding efficiency was favoured in mild acidic conditions. Similarly, a CDI concentration of about 0.63 mg/mg nanoparticles, acting during at least 1 h, provided binding efficiencies of about 50% bulk lectin. Under optimised experimental conditions, the DBA conjugates showed a size of around 500 nm and the amount of loaded carbazole and the DBA content were calculated to be around 15 and 23.5 microg/mg, respectively. The bioadhesive activity of NP and DBA conjugates was determined in samples of small and large rat intestinal mucosa. The amount of adsorbed NP was calculated to be around 8 and 4 g/m(2) in the small and large intestine, respectively. This high capacity to interact with the mucosa may be explained by gliadin composition. In fact, gliadin is rich in neutral and lipophilic residues. Neutral amino acids can promote hydrogen bonding interactions with the mucosa, while the lipophilic components can interact with the biological tissue by hydrophobic interactions. The bioadhesive activity of DBA conjugates was calculated to be about 2 g/m(2) in the small intestine and greater than 4 g/m(2) in the caecum and distal colon. These degrees of interaction were always significantly higher than those obtained with controls. Finally, DBA did not provide the specificity for interaction with Peyer's patches. In summary, gliadin nanoparticles show a high capacity of non-specific interaction with the intestine, whereas DBA binding to the surface of these carriers provided a greater specificity for colonic mucosa.

Adhesives↗

PubMed1999

Biodegradable cross-linked starch/protein microcapsules containing proteinase inhibitor for oral protein administration.

The objective of this study is to demonstrate the feasibility of microcapsules containing a protein and a proteinase inhibitor in order to allow the oral administration of proteic or peptidic drug. Starch/bovine serum albumin mixed-walled microcapsules were prepared using interfacial cross-linking with terephthaloyl chloride. The microcapsules were loaded with native or amino-protected aprotinin by incorporating protease inhibitors in the aqueous phase during the cross-linking process. Microcapsules can be degraded in the presence of alpha-amylase. The influence of the formulation parameters on the in vitro release of the inhibitor activity and the protein was studied. The protective effect of microcapsules with aprotinin for bovine serum albumin was revealed in vitro. The presence of the native bovine serum albumin was demonstrated after incubation of the microcapsules with aprotinin in a mixture of alpha-amylase (5.4 U/ml) and trypsin (900 spectrophotometric BAEE units/ml) for 3 h at 37 degrees C, whereas the protein was completely degraded in the release medium of the microcapsules without aprotinin.

Administration, Oral↗

PubMed1999

Cyclodextrins and carrier systems.

This paper describes two new possibilities of using cyclodextrins to increase water solubility and bioavailability of poorly water-soluble drugs intended for targeting delivery by the oral or the parenteral route. They use either amphiphilic cyclodextrin nanoparticles or polymeric nanoparticles containing cyclodextrins. Amphiphilic skirt-shaped cyclodextrins, resulting from the esterification of primary hydroxyl groups by hydrocarbon chains varying from C6 to C14, are capable of forming spontaneously nanoparticles which have been loaded with a series of steroid drugs. The drug in the amphiphilic cyclodextrin nanoparticles is molecularly dispersed and can be released very rapidly. Poly(isobutylcyanoacrylate) nanoparticles can be loaded with natural or hydroxypropyl cyclodextrins. This technique results in a significant increase in the loading capacity of nanoparticles with a series of steroids and in a very rapid release of the drug. Both methods are described as well as their potential interest for water-insoluble drugs.

Administration, Oral↗

PubMed1999

Cyclodextrins in targeting. Application to nanoparticles.

For some years cyclodextrins and their hydrophilic derivatives have been described in the literature as solubilizers capable of enhancing the loading capacity of liposomes and microparticles. We present here two new possibilities of using cyclodextrins in the design of colloidal carriers. The first possibility consists in increasing the loading capacity of poly(isobutyl cyanoacrylate) nanospheres prepared by anionic polymerization, by employing hydroxypropyl cyclodextrins. The second possibility consists in the spontaneous formation of either nanocapsules or nanospheres by the nanoprecipitation of amphiphilic cyclodextrin diesters. These two new techniques are very promising because of the great interest presented by nanoparticles for drug administration by the oral or parenteral routes.

Journal Article↗

PubMed1998

An original method for studying in vitro the enzymatic degradation of cross-linked starch microspheres.

A reproducible technique based on microvolume measurements has been described which can be used for the assessment of the enzymatic degradation of small samples of microspheres (typically 104 to 105 micrometer3). As a model, the degradation pattern of epichlorohydrin cross-linked starch microspheres by alpha-amylase has been studied in the range of 5 to 100 IU/l by this technique. On the one hand, analysis of the decrease in volume of the microspheres by a cubic root law suggested that the degradation profiles were dependent on the initial size distribution of the microspheres. On the other hand, no internal rupture of the microspheres was detected from size distribution data, suggesting that enzymatic degradation of starch microspheres is surface-controlled.

Cross-Linking Reagents↗

PubMed1998

In vitro studies on enhancing effect of sodium glycocholate on transbuccal permeation of morphine hydrochloride.

During the perioperative period, gastric emptying rate and first-pass metabolism limit the use of peroral morphine. Buccal mucosa appears to be a potential site for delivery of morphine as it provides direct entry into the system circulation thereby avoiding the hepatic first-pass effect. However, the low permeability of the buccal epithelium results in a low flux of the drug. The use of a penetration enhancer is required to improve the bioavailability of the drug via buccal route. In this study, the enhancing effect of sodium glycocholate (GC) used at 10 mM and 100 mM concentrations on permeation of morphine hydrochloride (MPH) across the porcine buccal mucosa was studied in vitro. Furthermore, in conjunction with its permeation, accumulation of GC in the tissue with time was also studied in order to elucidate the relationship between GC and enhanced mucosal permeation of the drug. Franz diffusion cells were used in the experiments. Permeation of MPH was increased in the presence of 100 mM GC with an enhancement factor of 9.3 whereas no enhancement was obtained with 10 mM GC. The calculated permeability coefficient for MPH in the presence of 100 mM GC was 2.35 x 10(-5) cm/s. Accumulation of GC at 100 mM in the tissue appears to be more significant at 100 mM concentration which correlated well with the increased permeation of the drug. GC was diffused through the buccal epithelium significantly at 100 mM concentration. Interaction of GC with the tissue appears to be more significant at 100 mM concentration compared to 10 mM concentration, thus resulting in a significant enhancing effect.

Analgesics, Opioid↗

PubMed1998

Combined poly(isobutylcyanoacrylate) and cyclodextrins nanoparticles for enhancing the encapsulation of lipophilic drugs.

PURPOSE: The aim of this study was to prepare and characterize nanoparticulate systems constituted of poly(isobutylcyanoacrylate) and cyclodextrins and intended for increasing the loading of the particles with lipophilic substances. Progesterone was used as a model substance. METHODS: Nanoparticles were prepared by polymerization of isobutylcyanoacrylate in presence of cyclodextrins or progesterone/ hydroxypropyl-beta-cyclodextrin complex. Particle size, zeta potential, cyclodextrin and progesterone loading of the particles were determined. RESULTS: Nanoparticles could be easily prepared in presence of cyclodextrins. An increase in hydroxypropyl-beta-cyclodextrin concentration resulted in small nanoparticles (less than 50 nm). It was found that large amounts of cyclodextrins remained associated to the particles, resulting in a 50 fold increase in progesterone loading compared to nanoparticles prepared in absence of cyclodextrins. CONCLUSIONS: The poly(isobutylcyanoacrylate)cyclodextrin nanoparticles were characterized by the presence of many lipophilic sites belonging to the cyclodextrins which were firmly anchored to the structure of the particles. Therefore, this new type of nanoparticles offers probably an opportunity for increasing the loading of nanoparticles with various lipophilic drugs.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1998

Evaluation of the hydrophobic drug loading characteristics in nanoprecipitated amphiphilic cyclodextrin nanospheres.

The aim of this work was to evaluate the loading capacity and the association characteristics of the hydrophobic drug progesterone on amphiphilic cyclodextrin nanospheres prepared by the nanoprecipitation method. The colloidal suspensions were prepared in the presence or absence of two different surfactants, Pluronic F68 and Tween 80. The physicochemical characteristics of the nanospheres were assessed using a nanosizer, zetameter, and transmission electron microscope. The physical state of the drug was verified using differential scanning calorimetry (DSC) and x-ray diffraction (XRD) methods. The in vitro progesterone release was investigated at 37 degrees C after dilution of the suspensions in sink conditions. Nanospheres with a mean diameter from 100 to 300 nm and a low degree of polydispersity were prepared from amphiphilic hexanoyl-gamma-cyclodextrin. The progesterone loading capacity was not affected by the formulation parameters tested. The DSC and XRD studies demonstrated the absence of the crystalline domains of progesterone in loaded nanospheres. The DSC studies also demonstrated the presence of interactions between the drug and carrier. The release of the drug from the carrier was extremely rapid and was governed by a partition phenomenon that depends only on the solubility of the drug in the release medium. From these results, we concluded that with this method, the progesterone is molecularly associated at the surface of the cyclodextrin nanospheres, probably through hydrophobic interactions in specific sites. The release profiles obtained can be of value when an improvement in the bioavailability of the drug is desired.

Calorimetry, Differential Scanning↗

PubMed1996

Bioadhesion of lectin-latex conjugates to rat intestinal mucosa.

PURPOSE: The specific interactions between three lectin-latex conjugates and different structures of rat intestinal mucosa have been studied ex vivo. METHODS: These systems were prepared by covalent coupling of different ligands, i.e., tomato lectin (TL), asparagus pea lectin (AL), mycoplasma gallisepticum lectin (ML), and bovine serum albumin (BSA) as control, to poly(styrene) latexes. RESULTS: Using mucosa samples without Peyer's patches (PP), the extent of interaction of all three lectin-latex conjugates with the mucosa decreased from duodenum to ileum, probably due to progressive diminution of the mucin concentration along the gastrointestinal tract. The following order of interaction of the conjugates with the mucus gel layer was observed: TL > ML = AL (p < 0.05). For each lectin, these results corresponded well to the concentration of its specific sugar in the mucus. Using intestinal samples with PP, an important increase of interaction of the conjugates with the mucosa was found for ML (about 25%) and AL (about 50%), whereas the interaction of TL decreased about 25%. CONCLUSIONS: Photomicrographs with fluorescent latexes have confirmed the specificity of the ML- and AL-latex conjugates for the PP region and of the TL-latex conjugates for the mucus gel.

Adhesives↗

PubMed1996

[Colonic irrigation for colostomies. Results of a national survey among 795 colostomized patients].

Colonic irrigation (CI) represents the procedure of choice for patients with a colostomy. Recent technical advances (irrigation kit) have provided patients with simple, safe and effective material, allowing a new expansion of this old concept. A total of 795 colostomates (from association's data base) were assessed by questionnaires 386 (49%) of them used CI: 43.5% of patients operated before 1980 and 50% after 1980 (p < 0.005). Two thirds of patients performed Cl every two days, in the morning, with one liter or less of water, for 45 to 60 minutes. No morbidity was reported. Some patients (18%) stopped the procedure deliberately, but none due to a complication. Total continence during 48 H was observed in 48.4% of patients. Wearing a classical stomabag after CI must be considered to be a precaution rather than a failure. However one half of patients wore a simplified material (minibag, obturator, sticking plaster). The vast majority of patients (86%) claimed to be entirely satisfied with CI and 96% wanted to continue the procedure as long as possible.

Adult↗

PubMed1994

Preparation and characterization of lectin-latex conjugates for specific bioadhesion.

This paper reports on the preparation and characterization of certain bioadhesive model drug deliver systems formed by a carrier (e.g. modified nanoparticles of polystyrene) and a ligand (e.g. tomato lectin, asparagus pea lectin, Mycoplasma gallisepticum lectin or albumin). Three different manufacturing methods (carbodiimide and glutaraldehyde coupling and physical adsorption) were studied. The activity of the lectin-latex conjugates and albumin-latex conjugate (control) were tested with gastric pig mucin. The manufacturing method had an insignificant effect on the activity, but all lectin-latex conjugates interacted two or three times more with mucin than with the control.

Adhesives↗

PubMed1994

Mucoadhesion of latexes. II. Adsorption isotherms and desorption studies.

Adsorption isotherms of poly(styrene) latexes on rat intestinal mucosa were studied under static conditions and analyzed according to different isotherm classifications. Isotherms of latexes with a particle size up to 670 nm had the characteristic shape of a disperse adsorbate on a porous adsorbent. Plateaus were reached at latex concentrations of about 2.5 g/L. The results indicated an increase in adsorption with the size and the hydrophilicity of the latexes. Typically, a surfactant-free carboxylate latex of 230 nm had a plateau of 0.66 g/m2, and a latex of 320 nm with added sodium dodecyl sulfate had a plateau of 0.881 g/m2. Surfactant-free carboxylate latex of 2 microns had a Langmuirian isotherm with a plateau level of 2.616 g/m2, which corresponded to a monolayer of adsorbed particles on the surface of mucosa. Desorption studies showed that the adsorption was irreversible. Adhesion to the mucous gel layer would therefore be limited by the mucus turnover.

Adsorption↗