Controlled Release of Doxorubicin from Doxorubicin/γ-Polyglutamic Acid Ionic Complex
Controlled Release of Doxorubicin from Doxorubicin/γ-Polyglutamic Acid Ionic Complex
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DOI：
10.1155/2010/780171
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发表时间：
2010-01-01
影响因子：
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通讯作者：
Margaritis, Argyrios
中科院分区：
文献类型：
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作者：
Manocha, Bhavik;Margaritis, Argyrios
通过离子相互作用形成药物/聚合物复合物已被证明对于药物的控制释放非常有效。这样的药物/聚合物离子复合物的稳定性可以受到溶液pH和离子强度的极大影响。目前工作的目的是评估γ-聚谷氨酸（γ-PGA）作为抗癌药物多柔比星（DOX）载体的潜力。我们研究了γ-PGA和DOX之间的离子复合物的形成，使用扫描电子显微镜，光谱，热分析和X-射线衍射。我们的研究表明，DOX特异性地与γ-PGA相互作用，形成随机胶体聚集体，并导致几乎100%的络合效率。体外药物释放研究表明，这些复合物在中性pH下相对稳定，但在酸性pH环境下解离缓慢，促进了DOX从复合物中的pH触发释放。还在生理缓冲液中评价了γ-PGA和DOX/γ-PGA复合物的水解降解。总之，这些研究清楚地显示了γ-PGA与阳离子药物如DOX缔合的可行性，这可能作为恶性组织中DOX控制释放的新药物载体。
Formation of drug/polymer complexes through ionic interactions has proven to be very effective for the controlled release of drugs. The stability of such drug/polymer ionic complexes can be greatly influenced by solution pH and ionic strength. The aim of the current work was to evaluate the potential of gamma-polyglutamic acid (gamma-PGA) as a carrier for the anticancer drug, Doxorubicin (DOX). We investigated the formation of ionic complexes between gamma-PGA and DOX using scanning electron microscopy, spectroscopy, thermal analysis, and X-ray diffraction. Our studies demonstrate that DOX specifically interacts with gamma-PGA forming random colloidal aggregates and results in almost 100% complexation efficiency. In vitro drug release studies illustrated that these complexes were relatively stable at neutral pH but dissociates slowly under acidic pH environments, facilitating a pH-triggered release of DOX from the complex. Hydrolytic degradation of gamma-PGA and DOX/gamma-PGA complex was also evaluated in physiological buffer. In conclusion, these studies clearly showed the feasibility of gamma-PGA to associate cationic drug such as DOX and that is may serve as a new drug carrier for the controlled release of DOX in malignant tissues.