Endogenous signal-responsive drug release from bioactive bone cement

骨质疏松性骨折在绝经后妇女中更常见，因为骨机械强度与反映钙和维生素D等营养因素的骨矿物质密度密切相关。由于具有雌激素活性的类固醇激素如雌二醇和雌酮被认为与骨吸收和骨形成的调节有关，绝经后的骨重建由于激素量的减少以及随后骨的矿物质密度的降低而变得相对不活跃。我们设计了一种使用生物相容性自固化磷酸钙骨水泥的几种药物的输送系统，该骨水泥在体内转化为羟基磷灰石。研究了去卵巢大鼠血浆钙水平对含雌二醇的自固化磷灰石骨水泥释放雌二醇的影响。骨水泥在含0.5和10 mg/100 mL钙的模拟体液中的体外释放曲线表明，随着溶出介质中钙浓度的增加，骨水泥的雌二醇释放速率降低，表明骨水泥的雌二醇释放依赖于缓冲液中的钙浓度。我们将这一发现应用于药物递送系统，并报道了皮下植入雌二醇负载骨水泥后，大鼠体内雌二醇释放量大于健康大鼠中观察到的雌二醇释放量，表明磷灰石骨水泥体内雌二醇释放依赖于血浆钙水平。

Osteoporotic fractures are observed more commonly among post-menopausal women, since bone mechanical strength is closely related to bone mineral density which reflects nutritional factors such as calcium and vitamin D.Since steroid hormones with estrogenic activity such as oestradiol and estron are considered to be related to the regulation of bone resorption and bone formation, bone remodeling after menopause becomes relatively inactive due to a decrease in the amount of hormone amount with the subsequent decrease in the mineral density of the bone. We designed a delivery system for several drugs using a biocompatible self-setting calcium phosphate cement which is transformed into hydroxyapatite in the body. The effect of plasma calcium levels on the oestradiol release from a self-setting apatite bone cement containing oestradiol in ovariectomized rats was investigated. The in-vitro release profiles from the cements in simulated body fluid containing 0.5 and 10mg/100mL calcium indicated that the oestradiol release rate decreased with increasing calcium concentration in dissolution media, suggesting that the in-vitro oestradiol release from apatite bone cement was dependent on the calcium concentration in the buffer. We applied this finding to the drug delivery system and reported that oestradiol release osteoporisi rats was greater than that observed in healthy rats after subcutaneous implantation of oestradiol-loaded cement, indicating that the in-vivo oestradiol release from apatite bone cement was dependent on plasma calcium levels.