Endogenous signal-responsive drug release from bioactive bone cement

生物活性骨水泥的内源信号响应药物释放

• 批准号: 08680946
• 负责人: OTSUKA Makoto
• 金额: $ 1.73万
• 依托单位: Kobe Pharmaceutical Univesity
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08680946/
• 关键词: Osteoporosis; Drug delivery system; apatite; biomaterials; sustained drug release; atificial bone; intelligent materials; bone mineral density; 骨粗鬆症,; 薬物送達システム,; アパタイト,; バイオマテリアル,; 徐放化,; 人工骨,; インテリジェントマテリアル,; 除放化

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.

骨质疏松性骨折在绝经后妇女中更为常见，因为骨的机械强度与骨密度密切相关，骨密度反映了钙和维生素d等营养因子。具有雌激素活性的类固醇激素，如雌二醇和雌二醇，被认为与骨吸收和骨形成的调节有关。绝经后的骨重塑变得相对不活跃，因为激素量的减少以及随后骨骼矿物质密度的减少。我们设计了一种药物递送系统，使用生物相容性的自固化磷酸钙水泥，它在体内转化为羟基磷灰石。研究了血浆钙水平对去卵巢大鼠含雌二醇的自凝磷灰石骨水泥中雌二醇释放的影响。骨水泥在含钙0.5 mg/100mL和10mg/100mL的模拟体液中的体外释放谱显示，雌二醇的释放率随溶出介质中钙浓度的增加而降低，提示磷灰石骨水泥体外释放雌二醇与缓冲液中钙浓度有关。我们将这一发现应用于给药系统，并报道了皮下植入雌二醇负载骨水泥后，骨质疏松大鼠的雌二醇释放量大于健康大鼠，这表明磷灰石骨水泥体内雌二醇释放依赖于血浆钙水平。

项目成果

M.OTSYKA,et al.: "Osteroporosis-Responsive Estradiol Release from Self-Seting Apatitic Bone Cement" Proceedings of the 23rd International Symposium on Controlled Release of Bioactive Matrials. 23. 186-187 (1996)

M.OTSYKA 等人：“自凝磷灰石骨水泥中的骨质疏松反应性雌二醇释放”第 23 届生物活性材料受控释放国际研讨会论文集。

M.Otsuka,et al.,: "Osteroporosis-Responsive Estradiol Release from Self-Seting Apatitic Bone Cement," Proceedings of the 23rd International Symposium on Controlled Release of Bioactive Matrials,. 23,. 186-187 (1996)

M.Otsuka 等人：“自凝磷灰石骨水泥中的骨质疏松反应性雌二醇释放”，第 23 届生物活性材料受控释放国际研讨会论文集。

M.Otsuka,et al.: "Effect of Micropore Structure on Drug Release from Self-Setting Calcium Phosphate Cement Containing Anti-Cancer Agent." Advanced Biomaterials in Biomedical Engineering and Drug Delivery Systems.1996. 367-368 (1996)

M.Otsuka 等人：“微孔结构对含抗癌剂的自凝磷酸钙水泥药物释放的影响”。

C.Hamasnishi, et al.: "A Self-Setting TTCP-DCPD Apatite Cement of Release of Vancomycin" Applied Biomaterials. 33. 139-143 (1996)

C.Hamasnishi 等人：“释放万古霉素的自凝 TTCP-DCPD 磷灰石水泥”应用生物材料。

M.Otsuka, et al.: "Effect of Micropore Structure on Drug Release from Self-Setting Calcium Phosphate Cement Containing Anti Cancer Agent" Advanced Biomaterials in Biomedical Engineering and Drug Delivery Systems. 1996. 367-368 (1996)

M.Otsuka 等人：“微孔结构对含有抗癌剂的自凝磷酸钙水泥释放药物的影响”生物医学工程和药物输送系统中的先进生物材料。