Complexation and release of doxorubicin from its complexes with pluronic P85-b-poly(acrylic acid) block copolymers.
Complexation and release of doxorubicin from its complexes with pluronic P85-b-poly(acrylic acid) block copolymers.
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DOI：
10.1016/j.jconrel.2007.05.010
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发表时间：
2007-08
期刊：
影响因子：
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通讯作者：
Y. Tian;L. Bromberg;S. N. Lin;T. Hatton;T. Hatton;K. Tam;K. Tam
中科院分区：
文献类型：
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作者：
Y. Tian;L. Bromberg;S. N. Lin;T. Hatton;T. Hatton;K. Tam;K. Tam
将聚丙烯酸（PAA）通过原子转移自由基聚合（ATRP）连接到Pluronic P85共聚物（EO27PO39EO27）的两端，制备了新型嵌段共聚物PAA-b-P85-b-PAA （P85PAA）。P85PAA - DOX复合物的形成和药物负载强烈依赖于PAA片段长度和pH，其中pH < 7.2时PAA片段中羧基的质子化减少了DOX在P85PAA链上的结合位点，导致低pH下DOX的摄取减少。pH 7.2时共聚物- DOX复合物的组成接近1:1的化学测量DOX：羧基摩尔比。证实了阳离子DOX分子和羧基之间静电相互作用的优势。对共聚物- dox配合物的稳定性研究表明，非多电解质相互作用也可能参与药物与P85PAA嵌段共聚物的络合作用。pH 5.0时DOX负载降低到总结合容量的60%，表明羧基的质子化降低了DOX与P85PAA嵌段共聚物的结合。DOX从配合物中释放是一个pH响应过程，其中羧基在弱酸性条件下的质子化导致共聚物-DOX配合物的更快解离，导致pH为5.0时DOX的加速释放。因此，DOX与P85PAA络合产生了一种药物递送系统，在pH 5.0的酸性环境中提供pH触发的DOX释放。
Poly(acrylic acid) (PAA) was attached on both termini of Pluronic P85 copolymer (EO27PO39EO27) via atom transfer radical polymerization (ATRP) to produce a novel block copolymer, PAA-b-P85-b-PAA (P85PAA). The P85PAA–DOX complex formation and drug loading were strongly dependent on the PAA segment length and pH, where the protonation of carboxyl groups in the PAA segment at pH < 7.2 reduced the binding sites of DOX onto P85PAA chains, resulting in a diminished DOX uptake at low pH. The composition of copolymer–DOX complexes at pH 7.2 was close to the stoichiometric 1:1 DOX:carboxyl molar ratio, confirming the dominance of electrostatic interactions between cationic DOX molecules and carboxyl groups. The stability study of the copolymer–DOX complex suggested that non-polyelectrolyte interactions may also participate in the complexation of drug and P85PAA block copolymer. DOX loading at pH 5.0 decreased to 60% of the total binding capacity, indicating that protonation of carboxyl groups reduced the DOX binding to P85PAA block copolymer. DOX release from the complex is a pH-responsive process, where the protonation of carboxyl groups at mildly acidic condition resulted in a faster dissociation of copolymer-DOX complex, leading to an accelerated release of DOX at pH 5.0. Thus, complexation of DOX with P85PAA yielded a drug delivery system affording a pH-triggered release of DOX in an acidic environment of pH 5.0.