Skeletal Drug Delivery System Research Articles

The efficacy of a hydroxyapatite composite as a biodegradable antibiotic delivery system.

Local biodegradable carriers have been studied for use as a skeletal drug delivery system. This study investigated the efficacy of a local biodegradable composite composed of hydroxyapatite, plaster of Paris, and chitosan impregnated with antibiotics to treat methicillin-resistant Staphylococcus aureus. The composite, impregnated with vancomycin, fosfomycin, or sodium fusidate was tested for its sustained elution characteristics during 3 months and compared with similarly impregnated polymethylmethacrylate using the modified disc diffusion technique. Physicochemical properties using scanning electron microscopy and xray diffraction analysis of each preparation also were analyzed. Vancomycin and fosfomycin incorporated into the hydroxyapatite composite inhibited the organism for 3 months, whereas sodium fusidate was effective only for 3 weeks. Vancomycin and fosfomycin loaded into the hydroxyapatite composite had a significantly better inhibitive effect than when loaded in polymethylmethacrylate, whereas sodium fusidate loaded in polymethylmethacrylate showed a significantly better inhibitive effect than when loaded in the hydroxyapatite composite. Scanning electron microscopy and xray diffraction analysis elucidated the patterns of each drug release profile. The local hydroxyapatite composite is a promising local biodegradable delivery system for vancomycin and fosfomycin, whereas PMMA is a better carrier for sodium fusidate in treating methicillin-resistant staphylococcus aureus osteomyelitis.

A novel skeletal drug delivery system using self-setting calcium phosphate cement VIII: the relationship between in vitro and in vivo drug release from indomethacin-containing cement

The relationship between in vitro and in vivo drug release from a self-setting bioactive calcium phosphate cement containing indomethacin (IMC) as a model drug was investigated. The in vitro IMC release rate from 1, 2 and 5% drug-loaded cement systems in simulated body fluid (SBF) at pH 7.25, 37°C increased with increase of drug concentration in the cement. The decreasing amount of calcium concentration in SBF during the drug release increased with increase of time. This was attributed to in vitro precipitation and/or growth of hydroxyapatite on the cement. The plasma IMC concentration and the area under the curve (AUC) from 1, 2 and 5% IMC-loaded cements after s.c. administration in rat depended on the loaded IMC concentration in the cements. The in vivo IMC release profiles from the cement were deconvoluted from the plasma IMC profiles after s.c. administration of IMC solution in rats. The relationship between in vitro release in SBF and the in vivo release profiles of 1, 2 and 5% IMC-loaded cements showed a straight line in the initial stage, but did not in the later stages.

A Novel Skeletal Drug Delivery System Using Self‐Setting Calcium Phosphate Cement. 9: Effects of the Mixing Solution Volume on Anticancer Drug Release from Homogeneous Drug-Loaded Cement

The effects of mixing solution volume (0.25–0.65 mL/g) on in vitro drug release from a self‐setting bioactive calcium phosphate cement containing the anticancer agent 6‐mercaptopurine (6‐MP) as a model compound were investigated. The drug release profiles from isolated planar surfaces as well as the entire surfaces of cement systems containing 5% 6‐MP were measured in simulated body fluid at pH 7.25 and 37.0 °C. The drug release rate from both cement system geometries increased with increasing mixing solution volume. Drug release profiles from the planar‐release and entire‐surface‐release cement matrix systems were analyzed by and found to agree with the Higuchi and Cobby equations, and the kinetic parameters were estimated with a nonlinear least‐squares computer program. Linear relationships were found between the mixing solution volume and the drug release rate constants or time required for 50% drug release for both cement release geometries. Furthermore, the total pore volume of the cements, as measured by mercury porosimetry, increased with increasing mixing solution volume.

自己硬化特性を有する生体活性セメントを用いた生体硬組織への薬物送達

自己硬化特性を有する生体活性セメントを用いた生体硬組織への薬物送達

A Novel Skeletal Drug Delivery System Using a Self‐Setting Calcium Phosphate Cement. 5 Drug Release Behavior from a Heterogeneous Drug-Loaded Cement Containing an Anticancer Drug

A novel drug delivery device based on a self‐setting bioactive calcium phosphate cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and testedin vitrousing the anticancer agent 6‐mercaptopurine (6‐MP) as a model compound. X‐ray diffraction results suggest that equimolar mixtures of the calcium phosphate salts were transformed into hydroxyapatite after being mixed with a dilute phosphoric acid solution, even in the presence of various amounts of 6‐MP powder. The inclusion of 6‐MP in the reaction mixture resulted in the formation of a homogeneous drug‐containing cement. Alternatively, the drug was loaded after cement formation to produce a heterogeneous drug‐containing pellet.In vitrodrug release from both the homogeneous and heterogeneous drug‐loaded cement pellets into simulated body fluid (pH 7.25, 37.0 °C) was measured using the rotating–disk method. Release from the homogeneous 5% drug‐loaded cements did not obey the Higuchi equation. The release rate from the heterogeneous drugloaded cements of different thicknesses (1, 2, and 3 mm) was a function of thickness, indicating that release kinetics could be controlled by the design of the cement formulation.

A novel skeletal drug delivery system using self-setting bioactive glass bone cement. III: the in vitro drug release from bone cement containing indomethacin and its physicochemical properties

Abstract A novel device containing indomethacin as a model drug using a self-setting bioactive cement based on CaOSiO 2 P 2 O 5 glass was investigated. Glass powders containing 2% and 5% indomethacin hardened within 5 min after mixing with a phosphate buffer. After setting, in-vitro drug release from homogeneous or heterogeneous drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37°C continued for more than 2 weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite and shrunk by about 5% in volume during the drug release test in SBF. Therefore, 30% of the loaded drug was extruded from the cement system at the initial stage, thereafter being released more slowly. Since the heterogeneous system consisting of the cement and the drug-loaded pellet avoided this effect, the drug was released more slowly than from the homogeneous drug-loaded cement. The heterogeneous system using the hardened cement after soaking in SBF at 37°C for 10 days released the drug very slowly at the initial stage since it avoided the drug squeezing effect, and the release continued slowly for more than 300 h.

A Novel Skeletal Drug-Delivery System Using Self-Setting Calcium Phosphate Cement. 4. Effects of the Mixing Solution Volume on the Drug-Release Rate of Heterogeneous Aspirin-Loaded Cement

The effect of the mixing solution volume was investigated on the in vitro drug-release rate of a novel drug-delivery device based on a self-setting bioactive calcium phosphate cement containing aspirin as a model drug. Equimolar mixtures of metastable calcium phosphate powders containing various proportions (3-40 w/w %) of seed hydroxyapatite crystals transformed into hydroxyapatite after being mixed with dilute phosphoric acid. The drug release from cement pellets in vitro into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C by the rotating disk method continued for more than 1 week. The drug-release rate from the cement increased with increasing volumes of mixing solution. The relationship between the liquid/powder ratio and the porosity of the cement was a straight line, indicating that the cement porosity depended on the amount of the mixing solution, but was independent of the amount of seed crystals. Drug release from the cement followed the modified Fick's law, with the rate increasing with the amount of mixing solution, since the porosity depended on the amount. The tortuosity of the cements was estimated from the modified Fick's equation, and the relationships between the drug release rate and the tortuosity of the pore in the drug-loaded cement in the plots were nonlinear. The results suggested that the drug-release rates from the cement were controlled by the drug diffusion in the pores.

A Novel Skeletal Drug Delivery System Using Self-Setting Bioactive Glass Bone Cement IV: Cephalexin Release From Cement Containing Polymer-Coated Bulk Powder

A novel device consisting of Eudragit-coated cephalexin as a model drug and a self-setting bioactive cement based upon CaO-SiO2-P2O5 glass was investigated. The glass cement hardened within 5 min of mixing with a phosphate buffer. After setting, in vitro drug release from homogeneous or heterogeneous drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for over 2 weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite and decreased in volume by about 5% during drug release in SBF. Consequently, 30% of the loaded drug was initially released from the homogeneous cement system, and thereafter it was released more slowly. Since the heterogeneous system consisting of the cement and a 50% polymer coated, drug-loaded pellet avoided this drug's burst, the drug was released over a longer period than that in the homogeneous system. The heterogeneous system released the polymer-coated drug very slowly, because it completely avoided the initial burst, and sustained the release over a long period.

New skeletal drug delivery system containing antibiotics using self-setting bioactive glass cement.

New skeletal drug delivery system containing antibiotics using self-setting bioactive glass cement.

A novel skeletal drug delivery system for anti-bacterial drugs using self-setting hydroxyapatite cement.

To solve the problem of delivering drugs to skeletal tissue at high enough local concentrations for desirable therapeutic effects, we report a novel approach using a self-setting hydroxyapatite cement, with cephalexin and norfloxacin as model drugs. After setting, the cement was transformed into hydroxyapatite with affinity for hard bone tissue. Continuous in-vitro drug release profiles from loaded cement pellets (0.9-4.8% by weight) in phosphate buffer at pH 7.4 and 37 degrees C followed the Higuchi equation.