Maree M David, Neuse Eberhard W, Erasmus Elizabeth, Swarts Jannie C
Department of Chemistry, University of the Free State, Bloemfontein 9300, South Africa.
Met Based Drugs. 2008;2008:217573. doi: 10.1155/2008/217573.
The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymers under mild coupling conditions has been achieved utilising the coupling reagent O-benzotriazolyl-N,N,N('),N(')-tetramethyluronium hexafluorophosphate to promote formation of the biodegradable amide bond. Even though the parent antineoplastic ferrocene and phthalocyanine derivatives are themselves insoluble in water at pH < 7, the new carrier-drug conjugates that were obtained are well water-soluble.
讨论了制备水溶性可生物降解药物载体的一般合成策略及其必须具备的性质。接着描述了赖氨酸和天冬氨酸的水溶性可生物降解共聚物作为潜在药物递送装置的合成，这些共聚物具有胺官能化侧链。利用偶联试剂O-苯并三唑基-N，N，N'，N'-四甲基脲六氟磷酸盐在温和的偶联条件下，实现了抗肿瘤二茂铁的羧酸衍生物和光动力活性酞菁部分与含胺药物载体共聚物的共价锚定，以促进可生物降解酰胺键的形成。尽管母体抗肿瘤二茂铁和酞菁衍生物本身在pH<7时不溶于水，但所得到的新型载体-药物共轭物具有良好的水溶性。
