Lu Zheng-Rong, Shiah Jane-Guo, Sakuma Shinji, Kopecková Pavla, Kopecek Jindrich
Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, UT 84112, USA.
J Control Release. 2002 Jan 17;78(1-3):165-73. doi: 10.1016/s0168-3659(01)00495-3.
This paper summarizes recent work on the design and development of targeted polymeric bioconjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. Polymerizable antibody Fab' fragment (MA-Fab') has been developed and used in the preparation of targeted HPMA copolymer-mesochlorin e6 conjugates for the treatment of human ovarian carcinomas. The reactivity of the MA-Fab' in copolymerization with HPMA depended on the length of the spacer between the monomer double bond and the antibody Fab' fragment. The biological activity of the antibody Fab' fragment was maintained after incorporation into the HPMA copolymer. Novel aromatic azo spacers were designed and incorporated into HPMA copolymer-drug (cyclosporin A, 9-aminocamptothecin) conjugates for the colon-specific drug delivery and for the treatment of colon diseases. The colon-specific drug release from the conjugates was controlled by the structures of both drug and spacers. Lectins, wheat germ agglutinin (WGA) and peanut agglutinin (PNA), were conjugated to the colon-specific polymer drug conjugates to enhance specific adhesion onto colon tissues.
本文总结了基于N-(2-羟丙基)甲基丙烯酰胺(HPMA)共聚物的靶向聚合物生物共轭物的设计与开发方面的近期工作。已开发出可聚合抗体Fab'片段(MA-Fab')，并将其用于制备靶向HPMA共聚物-间氯卟啉e6共轭物，用于治疗人类卵巢癌。MA-Fab'与HPMA共聚反应的活性取决于单体双键与抗体Fab'片段之间间隔臂的长度。抗体Fab'片段掺入HPMA共聚物后仍保持其生物活性。设计了新型芳香族偶氮间隔臂，并将其掺入HPMA共聚物-药物(环孢素A、9-氨基喜树碱)共轭物中，用于结肠特异性药物递送及结肠疾病的治疗。共轭物的结肠特异性药物释放受药物和间隔臂结构的控制。将凝集素，即麦胚凝集素(WGA)和花生凝集素(PNA)，与结肠特异性聚合物药物共轭物偶联，以增强对结肠组织的特异性黏附。
