Biomedical subjects

N Ubrich

Publications and source records attributed to N Ubrich.

13 recordsLinked to original sources

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

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↗

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

Protein encapsulation in biodegradable amphiphilic microspheres.

MPOE-PLA microspheres containing bovine serum albumin (BSA) were prepared by the double emulsion method with high encapsulation efficiency ( approximately 93%). Confocal scanning microscopic analysis using MPOE-PLA labelled with 1-pyrenemethanol showed the MPOE coating of the microsphere surface. This coating improves the performance of the release system compared with PLA microspheres; the hydrophilic chains reduce the BSA adsorption onto the microspheres and increase the amount of BSA released in the supernatant. Microsphere analysis using atomic force microscopy showed that the presence of the MPOE chains also leads to surface roughness. Studies of the diffusion of 1% rhodamine aqueous solution into the microspheres by means of confocal microscopy showed a fast diffusion of water through the matrices containing high molecular weight MPOE chains (?10 000 g mol-1) and could explain the fast release of BSA from these microspheres.

Adsorption↗

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↗

PubMed1997

Selective in vitro removal of anti-A antibodies by adsorption on encapsulated erythrocyte-ghosts.

Large volume plasma exchanges are used for the removal of anti-A or anti-B antibodies from the plasma of patients undergoing transplantation from donors with major ABO incompatibility. Previous works suggest that solid-phase immunoadsorption can be substituted for plasma exchange in situations where antigens can be purified and immobilized on columns through which plasma is percolated. However, the preparation of purified antigens of the ABO system is large quantities is laborious and requires the use of considerable blood volumes. Studies were therefore undertaken to determine the feasibility of an original immunoadsorbent based on porous microparticles prepared by a water/oil/water emulsification-solvent evaporation method, within which erythrocytes-ghosts carrying blood group antigens were entrapped. The decrease of the antibody hemagglutinating titre after adsorption onto encapsulated ghosts suggests that antibodies can cross the polymeric membrane and bind to the antigens. This original approach of using encapsulated antigens for the batchwise removal of antibodies could be extended to affinity chromatography, and immunoadsorption therapy with a chromatographic column linked to an extracorporeal circulation could be considered.

ABO Blood-Group System↗

PubMed1996

Antibodies released from immunoadsorbents: effect of support, activation and elution conditions.

Immunoadsorption is an application of affinity chromatography, as a therapeutic method to specifically deplete biological fluids such as blood plasma from proteins in excess, or to extract a biomolecule from a complex mixture. However, the leakage of small amounts of antibodies covalently immobilized on the support hampers the practical use of this method. In fact, these released antibodies contaminate the purified proteins or depleted media and, when they are of animal nature, they may lead to immunization of patients, or cause an anaphylactic shock when a clinical use is concerned. It is therefore of prime importance that the immunoadsorbents exhibit a satisfactory stability over the whole range of chemical and biochemical conditions involved during their clinical handling. To determine optimal conditions for the preparation of stable immunoadsorbents designed to remove selectively Low Density Lipoproteins (LDLs) from the plasma of patients affected by familial hypercholesterolemia, various immunoadsorbents were prepared by covalent immobilization of goat anti-apolipoprotein B polyclonal antibodies on different supports (Sepharose CL-4B, Sepharose 6 Fast Flow, Sphérodex and Fractogel) previously activated by various chemical reagents (cyanogen bromide, divinyl sulphone, tresyl chloride and trichloro-s-triazine). Their adsorption capacity, specificity, stability and the amount of immobilized antibodies were compared in terms of the activation method and the support used. It turns out that the immunoadsorbents prepared with Sepharose 6 Fast Flow lead to optimal yield of coupling, adsorption capacity, and an excellent stability at neutral pH. TC-activated-Fractogel turns out as well to afford an excellent coupling yield, a good adsorption capacity and an optimal stability in the whole pH range tested.

Adsorption↗

PubMed1992

Compared stability of Sepharose-based immunoadsorbents prepared by various activation methods.

During the use of chromatographic supports for the purification of proteins or the selective removal of substances by immunoaffinity, leakage of the antibodies immobilized on the matrix is systematically observed. When the cleansing of blood plasma by extracorporeal circulation is concerned, it is of prime importance that the immunoadsorbents exhibit an extensive chemical stability over the whole range of experimental conditions. To study and minimize this leakage, a matrix, Sepharose CL-4B, was activated by various chemical reagents and coupled to goat anti-apolipoprotein B polyclonal antibodies. Immunoadsorbents thus prepared were compared with those obtained earlier by cyanogen bromide activation. It turns out that divinyl sulphone- and tresyl chloride-activated supports lead to similar results in terms of coupling yield and adsorption capacity, but to a significant reduction in released antibodies.

Animals↗

PubMedDate not supplied

Importance of the matrix and its chemical activation on the stability of immuno-adsorbents.

Various matrices were reacted with four different activation reagents, in order to prepare immuno-adsorbents for the selective removal of low-density lipoproteins from blood plasma of patients affected by hypercholesterolaemia. The resulting immuno-adsorbents were compared to that obtained earlier with cyanogen bromide activation, in terms of coupling yield, adsorption capacity and moreover stability towards the various chemical and biochemical conditions to which they are submitted during their handling. Tresyl chloride-activated Sepharose 6 Fast Flow turns out to afford optimal stability in the whole pH range tested.

Chromatography, Affinity↗

PubMedDate not supplied

Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles.

Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation efficiency and heparin release profiles were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation efficiency was observed when 5000 IU of heparin were incorporated in the first emulsion. High drug entrapment efficiency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (<14%). The use of the two types of Eudragit in combination with PCL and PLAGA increased the encapsulation efficiency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modified and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a significant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.

Biodegradation, Environmental↗