Design of novel bioconjugates for targeted drug delivery

J Control Release. 2002 Jan 17;78(1-3):165-73. doi: 10.1016/s0168-3659(01)00495-3.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Colonic Diseases / drug therapy*
  • Drug Delivery Systems*
  • Drug Design
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / administration & dosage
  • Methacrylates / administration & dosage*
  • Ovarian Neoplasms / drug therapy*

Substances

  • Immunoglobulin Fab Fragments
  • Methacrylates
  • hydroxypropyl methacrylate