Guise V, Drouin J Y, Benoit J, Mahuteau J, Dumont P, Couvreur P
Laboratoire de Pharmacie Galénique UA CNRS 1218, University of Paris, France.
Pharm Res. 1990 Jul;7(7):736-41. doi: 10.1023/a:1015819706491.
The chemical reaction of vidarabine (VIDA) with isohexyl cyanoacrylate nanoparticles in a pH-dependent fashion occurs only in the presence of dioctylsulfosuccinate (DOSS). The formation of an ion pair with DOSS allows a better contact of VIDA with the monomer during the polymerization process taking place in micelles. On the basis of molecular weight profiles of the polymer, determined by gel permeation chromatography (GPC), it is proposed that VIDA induces the polymerization of cyanoacrylic monomers through a zwitterionic pathway. This mechanism allows the covalent linkage of the drug with the polymer, which is consistent with NMR experiments. The present study illustrates the need for physicochemical studies in the design of new colloidal drug delivery formulations.
阿糖腺苷(VIDA)与异己基氰基丙烯酸酯纳米颗粒的化学反应以pH依赖的方式发生,且仅在存在二辛基磺基琥珀酸酯(DOSS)的情况下才会出现。与DOSS形成离子对能使VIDA在胶束中发生的聚合过程中更好地与单体接触。根据通过凝胶渗透色谱法(GPC)测定的聚合物分子量分布,提出VIDA通过两性离子途径诱导氰基丙烯酸单体聚合。该机制使药物与聚合物发生共价连接,这与核磁共振实验结果一致。本研究表明在新型胶体药物递送制剂设计中进行物理化学研究的必要性。