Preparation and characterization of biodegradable polyhydroxybutyrate-co-hydroxyvalerate/polyethylene glycol-based microspheres.
The in vivo effectiveness of biomolecules may be limited by their rapid diffusion in the body and short half-life time. Encapsulation of these biomolecules allows protecting them against degradation and ensuring a controlled release over time. In this work, the production of polyhydroxybutyrate-co-hydroxyvalerate/polyethylene glycol-based microspheres loaded with heparin by double emulsion-solvent evaporation is investigated. Significant improvements are achieved after blending PHB-HV microspheres with PEG. First of all, an important decrease of the initial burst effect is ensured. Moreover, lower degradation of the microspheres is observed after 30days in the release medium. Finally, the release rate could be controlled using different PEG molecular weights and concentrations. A toxic effect of PHB-HV 30% PEG 1100gmol-1microspheres is observed whereas PHB-HV and PHB-HV 30% PEG 10,000gmol-1microspheres are not toxic. These microspheres seem to be most suited for further tissue engineering applications. The effectiveness of direct PEG blending to PHB-HV is proved, limiting the use of chemical reagents for PHB-HV/PEG copolymer synthesis and steps for chemical reagents removal from the copolymer.
Université de Lyon, Univ. Lyon 1, CNRS, CPE, UMR 5007, Laboratoire d'Automatisme et de Génie des procédés (LAGEP), 43 Bd du 11 Novembre 1918, F-69616 Villeurbanne, France.
Alexandre
A
Monnier
Aix Marseille Université, CNRS, ISM UMR 7287, Marseille, France.
Charlotte
C
Rombouts
Université de Lyon, Univ. Lyon 1, CNRS, CPE, UMR 5007, Laboratoire d'Automatisme et de Génie des procédés (LAGEP), 43 Bd du 11 Novembre 1918, F-69616 Villeurbanne, France.
Dania
D
Kouider
Aix Marseille Université, CNRS, ISM UMR 7287, Marseille, France.
Imad
I
About
Université de Lyon, Univ. Lyon 1, CNRS, CPE, UMR 5007, Laboratoire d'Automatisme et de Génie des procédés (LAGEP), 43 Bd du 11 Novembre 1918, F-69616 Villeurbanne, France.
Hatem
H
Fessi
Université de Lyon, Univ. Lyon 1, CNRS, CPE, UMR 5007, Laboratoire d'Automatisme et de Génie des procédés (LAGEP), 43 Bd du 11 Novembre 1918, F-69616 Villeurbanne, France. Electronic address: monnier@lagep.univ-lyon1.fr.
Nida
N
Sheibat-Othman
D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D065546:Drug Liberation; D004655:Emulsions; D006493:Heparin / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008863:Microspheres; D008970:Molecular Weight; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D000091402:Prohibitins; D012997:Solvents / Q000737:chemistry; D013997:Time Factors; D000094122:Polyhydroxybutyrates
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D006493:Heparin; D011091:Polyesters; D011092:Polyethylene Glycols; D000091402:Prohibitins; D012997:Solvents; C000717328:PHB protein, human; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates
Double-emulsion; Drug release; Microencapsulation; Polyethylene glycol; Polyhydroxybutyrate-co-hydroxyvalerate; Toxicity