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Biomedical subjects

M C Lévy

Publications and source records attributed to M C Lévy.

7 recordsLinked to original sources
PubMed2000

Cross-linked beta-cyclodextrin microcapsules: preparation and properties.

Microcapsules were prepared by interfacial cross-linking of beta-cyclodextrins (beta-CD) with terephthaloyl chloride (TC). Batches were prepared from beta-CD solutions in 1 M NaOH, using 5% TC and a 30 min reaction time. Microcapsules were studied with respect to morphology (microscopy), size (laser diffraction technique) and, for selected batches, IR spectroscopy, determination of beta-CD content (polarimetry after alkaline dissolution of microcapsules) and complexing properties, evaluated using p-nitrophenol (pNP) as the guest molecule. Well-formed microcapsules were obtained from 5, 7.5, and 10% beta-CD solutions. The mean size of all batches was in the 10-35 microm range. The IR spectrum showed bands at 1724, 1280 and 731 cm(-1), reflecting the formation of esters. The beta-CD contents were 46, 56-58 or 60-66% for batches prepared from 5, 7.5 or 10% beta-CD solutions, respectively. The experiments conducted with 1 mM pNP showed a rapid complexation reaching a maximum within 1 h. When incubating 50 mg lyophilized microcapsules in 10 ml pNP solution, the maximal fixation (97.8 micromol/g microcapsules) was observed for small-sized particles ( approximately 11 microm) prepared from a 7.5% beta-CD solution. The method then appears as a simple and rapid procedure to provide stable microcapsules, having an interesting guest-binding ability.

Capsules↗
PubMed1999

Serum albumin-alginate coated beads: mechanical properties and stability.

According to a previously described method, alginate beads were prepared from a Na-alginate solution containing propylene glycol alginate (PGA) and human serum albumin (HSA). The solution was added dropwise to a CaCl2 solution. The beads were treated with NaOH, which started the formation of amide bonds between HSA and PGA at the periphery, giving a membrane. Batches of beads with increasingly thick membranes were prepared using growing concentrations of NaOH, and studied with a texture analyser. When raising NaOH concentration, the rupture strength progressively increased, and the resistance strength to a deformation of 50% of total height also increased before slightly decreasing for the highest NaOH concentration. Variations of bead elasticity were also observed. When the beads were prepared with saline reducing gelation time from 10 to 5 min, and reaction time from 15 to 5 min, mechanical properties varied more progressively with the NaOH concentration, while the results became more reproducible. A series of assays conducted with 0.01 M NaOH confirmed the importance of using a short gelation time, and saline rather than water. Stability assays were also performed. The results were compared to those of alginate-polylysine coated beads and showed the interest of the transacylation method.

Alginates↗
PubMed1999

In-vivo delivery of therapeutic proteins by genetically-modified cells: comparison of organoids and human serum albumin alginate-coated beads.

We have designed a self-assembling multimeric soluble CD4 molecule by inserting the C-terminal fragment of the alpha chain of human C4-binding protein (C4bp alpha) at the C-terminal end of human soluble CD4 genes. This CD4-C4bp alpha fusion protein (sMulti-CD4) and two other reference molecules, a fusion protein of human serum albumin (HSA) and the first two domains of CD4 (HSA-CD4) and monomeric soluble CD4 (sMono-CD4), were delivered in vivo by genetically modified 293 cells. These cells were implanted in mice as organoids and also encapsulated in HSA alginate-coated beads. sMulti-CD4 showed an apparent molecular weight of about 300-350 kDa, in accordance with a possible heptamer formula. sMulti-CD4 produced either in cell culture or in vivo in mice appeared to be a better invitro inhibitor of HIV infection than sMono-CD4. Plasma levels of sMulti-CD4, HSA-CD4, and sMono-CD4 reached approximately 2,300, 2,700, and 170 ng/mL, respectively, 13 weeks after in-vivo organoid implantation, which had formed tumours at that time. This suggests that the plasma half-life of sMulti-CD4 is much longer than that of sMono-CD4. The 293 xenogeneic cells encapsulated in HSA alginate-coated beads remained alive and kept secreting sMono-CD4 or HSA-CD4 continuously at significant levels for 18 weeks in nude mice, without tumour formation. When implanted in immunocompetent Balb/c mice, they were rejected two to three weeks after implantation. In contrast, encapsulated BL4 hybridoma cells remained alive and kept secreting BL4 anti-CD4 mAb for at least four weeks in Balb/c mice. These results suggest the clinical potential of the C4bp-multimerizing system, which could improve both the biological activity and the poor in-vivo pharmacokinetic performance of a monomeric functional protein like soluble CD4. These data also show that a systemic delivery of therapeutic proteins, including immunoglobulins, can be obtained by the in-vivo implantation of engineered allogeneic cells encapsulated in HSA alginate-coated beads.

Alginates↗
PubMed1982

Microencapsulation III: Preparation of invertase microcapsules.

Invertase was incorporated into polyamide microcapsules. The following parameters were studied: pH of the aqueous phase during interfacial polymerization; duration of the polymerization; surfactant concentration; stirring rate; improvements in the isolation procedure; effect of lyophilization. The inactivation of the encapsulated enzyme by pepsin was shown to be related to the acidic incubation medium and prompted incorporation of protective proteins in the microcapsules. This process allowed relative protection of the enzyme. In a second set of experiments, an emulsification-reticulation method was developed, which encapsulated invertase in a cross-linked protein. Various proteins and bifunctional acylating agents were tested. Microcapsules of immobilized invertase were prepared through cross-linking of the enzyme protein itself.

Capsules↗
PubMed1982

Microencapsulation IV: Cross-linked hemoglobin microcapsules.

Hemoglobin microcapsules were prepared through cross-linking of hemoglobin itself with various acyldichlorides. Variations in the reticulation conditions were preformed in order to ameliorate the oxygen dissociation curve, the mean diameter, and the possibility for the microcapsules to be lyophilized. With terephthaloylchloride, as the cross-linking agent, incorporation of inositol hexaphosphate and glucose, followed by stabilization through glutaraldehyde and using high stirring speed, allowed preparation of stable hemoglobin microcapsules, 5 micrometers in diameter, which suffered rapid lysis by proteases. They were able to ensure oxygen transfer: the dissociation curve was sigmoidal with a p50 = 13 mm Hg. They retained these properties after lyophilization followed by rehydration.

Capsules↗
PubMedDate not supplied

[Microcapsules with modulable properties made with cross-linked proteins and polysaccharides].

A cross-linking process was applied to mixtures of a protein (gelatin A or B) and a polysaccharide. Mixed-walled microcapsules were then obtained, which exhibited properties different from those of microcapsules prepared from the protein alone. They were shown to be more resistant to enzymatic lysis and this effect depended on the ratio of the polysaccharide, on its nature and on the cross-linking pH. Very hydrophilic microcapsules were obtained through cross-linking of gelatin admixed with alginate or carboxymethylcellulose. The addition of alginate to gelatin resulted in a slower release of encapsulated pilocarpine.

Delayed-Action Preparations↗