Bodhibukkana Chatchada, Srichana Teerapol, Kaewnopparat Sanae, Tangthong Naruedom, Bouking Pisit, Martin Gary P, Suedee Roongnapa
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai, Songkla 90112, Thailand.
J Control Release. 2006 Jun 12;113(1):43-56. doi: 10.1016/j.jconrel.2006.03.007. Epub 2006 Mar 20.
A composite membrane for transdermal delivery of S-propranolol enantiomer was developed based on the controlled pore functionalization of bacterial cellulose membranes using a molecularly imprinted polymer (MIP) layer synthesis. The reactive pore-filling of an asymmetric porous cellulose membrane with a MIP thin-layer was effected using a silanized coupler as an additional anchor for the MIP. MIP thin-layers with specific binding sites for S-propranolol were synthesized by copolymerization of methacrylic acid with a cross-linker, ethylene glycol dimethacrylate in the presence of S-propranolol as the template molecule and the latter was subsequently extracted. Selective transport of S-propranolol through the MIP composite membrane was obtained, although this was determined mostly by the parent cellulose membrane with some ancillary contributory effect from the MIP layer. In addition, an enantioselectivity in the transport of propranolol prodrug enantiomers was found, suggesting that the shape and functional groups orientation, which are similar to that of the print molecule were essential for enantiomeric recognition of the MIP composite membrane. The enantioselectivity of S-MIP membranes was also shown when the release of propranolol enantiomers was studied in vitro using rat skin, with racemic propranolol contained in the donor compartment. The composite membrane of bacterially-derived cellulose and molecularly imprinted polymer may have great potential for use as a transdermal enantioselective controlled-release system for racemic propranolol.
基于利用分子印迹聚合物(MIP)层合成对细菌纤维素膜进行可控孔功能化,开发了一种用于透皮递送S-普萘洛尔对映体的复合膜。使用硅烷化偶联剂作为MIP的额外锚定物,通过MIP薄层对不对称多孔纤维素膜进行反应性孔填充。在S-普萘洛尔作为模板分子存在的情况下,通过甲基丙烯酸与交联剂乙二醇二甲基丙烯酸酯共聚合成具有S-普萘洛尔特异性结合位点的MIP薄层,随后萃取模板分子。获得了S-普萘洛尔通过MIP复合膜的选择性转运,不过这主要由母体纤维素膜决定,MIP层有一些辅助作用。此外,发现普萘洛尔前药对映体在转运过程中具有对映选择性,这表明与印迹分子相似的形状和官能团取向对于MIP复合膜的对映体识别至关重要。当在体外使用供体隔室中含有外消旋普萘洛尔的大鼠皮肤研究普萘洛尔对映体的释放时,也显示了S-MIP膜的对映选择性。细菌衍生纤维素与分子印迹聚合物的复合膜作为外消旋普萘洛尔的透皮对映选择性控释系统可能具有巨大潜力。