title: The effect of porosity on drug release kinetics from vancomycin microsphere/calcium phosphate cement composites.
abstract: The influence of porosity on release profiles of antibiotics from calcium phosphate composites was investigated to optimize the duration of treatment. We hypothesized, that by the encapsulation of vancomycin-HCl into biodegradable microspheres prior admixing to calcium phosphate bone cement, the influence of porosity of the cement matrix on vancomycin release could be reduced. Encapsulation of vancomycin into a biodegradable poly(lactic co-glycolic acid) copolymer (PLGA) was performed by spray drying; drug-loaded microparticles were added to calcium phosphate cement (CPC) at different powder to liquid ratios (P/L), resulting in different porosities of the cement composites. The effect of differences in P/L ratio on drug release kinetics was compared for both the direct addition of vancomycin-HCl to the cement liquid and for cement composites modified with vancomycin-HCl-loaded microspheres. Scanning electron microscopy (SEM) was used to visualize surface and cross section morphology of the different composites. Brunauer, Emmett, and Teller-plots (BET) was used to determine the specific surface area and pore size distribution of these matrices. It could be clearly shown, that variations in P/L ratio influenced both the porosity of cement and vancomycin release profiles. Antibiotic activity during release study was successfully measured using an agar diffusion assay. However, vancomycin-HCl encapsulation into PLGA polymer microspheres decreased porosity influence of cement on drug release while maintaining antibiotic activity of the embedded substance.
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-University Marburg, Ketzerbach 63, 35032 Marburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schnieders
authors.forename: Uwe
authors.initials: U
authors.lastname: Gbureck
authors.forename: Elke
authors.initials: E
authors.lastname: Vorndran
authors.forename: Michael
authors.initials: M
authors.lastname: Schossig
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001843:Bone Cements / Q000737:chemistry*; D002130:Calcium Phosphates / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D006801:Humans; D006882:Hydroxyapatites; D007700:Kinetics; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008863:Microspheres; D010019:Osteomyelitis / Q000188:drug therapy; D016062:Porosity; D011208:Powders; D013211:Staphylococcus aureus / Q000378:metabolism; D014640:Vancomycin / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D002130:Calcium Phosphates; D006882:Hydroxyapatites; D011208:Powders; D014640:Vancomycin; C020243:calcium phosphate