Biomedical subjects

M Rebuelta

Publications and source records attributed to M Rebuelta.

7 recordsLinked to original sources

PubMed2001

Modulated release of cyclosporine from soluble vinyl pyrrolidone--hydroxyethyl methacrylate copolymer hydrogels. A correlation of 'in vitro' and 'in vivo' experiments.

Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of the immunosuppressor cyclosporine. Two copolymeric systems with copolymer compositions f(VP)=0.52 (namely VP--HEMA 60--40) and 0.42 (VP--HEMA 40--60) have been prepared and tested in vitro and in vivo using rats as animal model. Micellar electrokinetic capillary chromatography, MEKC, has been used for the simultaneous detection of the polymer reabsorption and the drug release for the in vitro experiments. The composition and microstructural distribution of the copolymer system controls the solubilization rate which modulates the in vitro release of the drug (with time profiles from a few days to several weeks for the VP--HEMA 60--40 and 40--60, respectively) and the in vivo response that correlates with the previous in vitro results: the more hydrophobic implant (VP--HEMA 40--60) reverts the immune response more slowly (2--4 weeks) compared to the more hydrophilic one (VP--HEMA 60--40, 1--2 weeks).

Animals↗

PubMed2000

Controlled release of cyclosporine from VP-HEMA copolymer systems of adjustable resorption monitorized by MEKC.

Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of drugs, taking cyclosporine as a model system. The copolymerization parameters described as reactivity ratios, rVP = 0.08 and rHEMA = 7.97, indicate that the copolymer systems prepared at high conversion have two main components with a microstructural arrangement which depends on the average composition, i.e., an initial HEMA-rich copolymer and a final PVP homopolymer or VP-rich copolymer. This microstructural distribution controls the resorption rate of the polymeric support and therefore the release process of cyclosporine which is demonstrated experimentally by the application of a modern technique known as micellar electrokinetic capillary chromatography (MEKC).

Chromatography, Micellar Electrokinetic Capillary↗

PubMed2000

Recombinant growth hormone delivery systems based on vinylpyrrolidone-hydroxyethyl methacrylate copolymer matrices: monitoring optimization by capillary zone electrophoresis.

Experimental conditions for the fabrication of two new polymeric devices (i.e. films and slabs) useful for the controlled release of recombinant growth hormone (GH) are given. The release rate is controlled by the resorption profile of the vinylpyrrolidone-hydroxyethyl methacrylate (VP-HEMA) tested systems which is related to the copolymer composition. The suitability of capillary electrophoresis (CE) for following the complete preparation of the different VP-HEMA devices is shown. Moreover, CE allows simultaneous monitoring of the controlled release of GH and dissolved polymer during in vitro experiments. From these results, guidelines are given for the fabrication of polymeric devices containing protein as active drug as well as for the correct selection of conditions during in vitro experiments.

Biocompatible Materials↗

PubMed1999

New resorbable polymeric systems with antithrombogenic activity.

The synthesis and application as resorbable coatings of vascular grafts of a new polyacrylic derivative of Triflusal (2-acetyloxy-4-trifluoromethyl)benzoic acid, a commercial drug with antithrombogenic properties, are described. The high-molecular-weight polyacrylic system is rather stable in physiological conditions and provides a chemical support for the slow release of the pharmacologically active compound, Triflusal, or its main metabolite (2-hydroxy-4-trifluoromethyl)benzoic acid (HTB). Experiments of deposition and retention of platelets in static basal conditions using plasma-rich medium from blood of sheep, seem to indicate that the polymeric coating of the polyacrylic derivative of Triflusal improves the antiaggregating character for platelets of the surface of small-diameter vascular grafts without the application of other antithrombogenic drugs.

Journal Article↗

PubMed1997

Application of tertiary amines with reduced toxicity to the curing process of acrylic bone cements.

4-Dimethylaminobenzyl alcohol (DMOH) and 4-dimethylaminobenzyl methacrylate (DMMO) were used as the activators in the benzoyl peroxide initiated redox polymerization for the preparation of acrylic bone cement based on poly(methylmethacrylate) beads of different particle size. The residual monomer content of the cured cements was about 2 wt %, independent of the redox system used in the polymerization, indicating that the activating effect of the tertiary aromatic amines DMOH or DMMO was sufficient to reach a polymerization conversion similar to that obtained with the benzoyl peroxide (BPO) N,N-dimethyl-4-toluidine (DMT) system. The BPO/DMOH and BPO/DMMO redox systems provided exotherms of decreasing peak temperature and increasing setting time, and the cured materials presented higher average molecular weight and similar glass transition temperatures in comparison with those obtained when DMT was used as the activator. In addition, these activators are three times less toxic than the classical DMT.

Acrylates↗

PubMed1997

Analysis of the leaching and toxicity of new amine activators for the curing of acrylic bone cements and composites.

The comparative reactivity of new tertiary amine activators with the basic chemical structure of N,N-dimethyl-4-toluidine, but reduced toxicity, is analysed. The leaching of the amine compounds from cured cements was studied by analysis of the concentration of the corresponding amine in a physiological saline solution after 3 months of immersion, giving lower values for the new amine compounds as compared to N,N-dimethyl-4-toluidine. The acute toxicity was determined by intravenous injection of saline solutions of the corresponding chlorhydrates in mice and the cytotoxicity by the evolution of specific culture media. The results obtained demonstrate a lower acute toxicity and cytotoxicity of the new activators, even with a noticeable antiseptic action, which makes these materials very interesting from a practical point of view as activators of the curing process of acrylic bone cements for orthopaedic surgery and dentistry.

Acrylic Resins↗

PubMed1996

Polymeric drugs derived from ibuprofen with improved antiinflammatory profile.

A new methacrylic monomeric compound bearing Ibuprofen (MIA) and the respective polymethacrylic macromolecular derivative (polyMIA) were evaluated for antiinflammatory properties in order to study their pharmacological activity profile. The macromolecular drug is constituted of Ibuprofen residues linked covalently to a polymethacrylic support, as a side substituent of the repeating unit, by means of a spacer group (p-aminophenoxy) that, in addition, is the most representative metabolite of Paracetamol. The Ibuprofen is slowly released from the polymeric support by hydrolysis of the ester bond in a biological medium. Different antiinflammatory testing methods were used; and the results obtained indicate that the monomeric and polymeric forms display higher potency to inhibit acute inflammatory processes than the traditional Ibuprofen form, even doubling the power of Ibuprofen. In addition, they present higher activity against chronic experimental processes, as well as an excellent antinociceptive behavior to inhibit the pain associated with arthritic diseases. According to previous reports and results presented in this article, we can conclude that the new polymethacrylic structures show higher analgesic, antipiretic, and antiinflammatory activities due to the possible activity of the macromolecular drug as well as to the controlled Ibuprofen release from the macromolecular delivery system. After releasing of the side active residue, a derivate of poly(sodium methacrylate) is formed, which is cleared from the body easily by the normal pathway of kidney metabolism.

Analgesics↗