Molecular Recognition Materials Research Unit, Drug Delivery System Excellence Center, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai, Songkla 90112, Thailand.
J Control Release. 2010 Feb 25;142(1):122-31. doi: 10.1016/j.jconrel.2009.10.011. Epub 2009 Oct 23.
This study aimed to develop enantioselective-controlled drug delivery systems for selective release of the required (S)-enantiomer in a dose formulation containing a racemic drug in response to pH stimuli. The recognition system was obtained from a nanoparticle-on-microsphere (NOM) molecularly imprinted polymer (MIP) with a multifunctional chiral cinchona anchor synthesised by suspension polymerisation using ethylene glycol dimethacrylate as a cross-linker. (S)-omeprazole was used as an imprinting molecule conferring stereoselectivity upon the polymers. The ability of the prepared recognition polymers to selectively rebind (S)-omeprazole was evident at different pH levels (the highest being at pH 7.4). The partial selective-release phenomenon of the (S)-enantiomer in MIP-containing composite cellulose membranes with increased vehicular racemic omeprazole concentrations was highly pH-dependent. Cinchona-bonded polymers imprinted with (S)-omeprazole could recognise the moldable contact site of (S)-omeprazole independently of its chirality; this is responsible for the delivery of (S)-enantiomer from racemic omeprazole. The controlled-release drug devices were fabricated with synthesised composite latex, and consisted of a pH stimuli-responsive poly(hydroxyethyl methacrylate) (HEMA) and polycaprolactone-triol (PCL-T) blend, and a MIP with preloaded drug, along with pH 7.4 buffer in the device's interior. The results demonstrate that drug delivery systems containing (S)-omeprazole imprinted cinchona-polymer nanoparticle-on-microspheres may maximise efficacy while minimising dose frequency.
本研究旨在开发对映体控制的药物传递系统，以在包含外消旋药物的剂量配方中响应 pH 刺激选择性释放所需的 (S)-对映异构体。识别系统是通过悬浮聚合使用乙二醇二甲基丙烯酸酯作为交联剂合成的具有多功能手性金鸡纳锚的纳米颗粒-微球 (NOM) 分子印迹聚合物 (MIP) 获得的。(S)-奥美拉唑被用作印迹分子，赋予聚合物对映体选择性。在不同 pH 值下（最高为 pH 7.4），制备的识别聚合物对 (S)-奥美拉唑选择性再结合的能力明显。在含有载体外消旋奥美拉唑浓度增加的 MIP 复合纤维素膜中，(S)-对映体的部分选择性释放现象高度依赖 pH 值。用 (S)-奥美拉唑印迹的金鸡纳键聚合物可以独立于其手性识别可塑接触位点的 (S)-奥美拉唑；这是负责从外消旋奥美拉唑中输送 (S)-对映体的原因。用合成的复合乳液制造了控释药物装置，该乳液由对 pH 刺激敏感的聚 (羟乙基甲基丙烯酸酯) (HEMA) 和聚己内酯三醇 (PCL-T) 共混物以及载有药物的 MIP 以及装置内部的 pH 7.4 缓冲液组成。结果表明，含有 (S)-奥美拉唑印迹金鸡纳聚合物纳米颗粒-微球的药物传递系统可以在最大程度地提高疗效的同时最小化剂量频率。
