Targetable polymeric prodrugs |
| |
| Institution: | 1. Institute of Macromolecular Chemistry, Czechoslovak Academy of Sciences, 16206 Prague 6, Czechoslovakia;2. Departments of Pharmaceutics and Bioengineering, University of Utah, Salt Lake City, UT 84112 U.S.A.;1. Department of Materials Science & Engineering, Myongji University, Yongin 17058, South Korea;2. Department of Materials Science & Engineering, Seoul National University, Seoul 08826, South Korea;3. Department of Materials Science & Engineering, Ajou University, Suwon 16499, South Korea;4. Department of Energy Systems Research, Ajou University, Suwon 16499, South Korea;1. Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, USA;2. Department of Veterinary Microbiology, University of Ilorin, Ilorin, Nigeria;1. Department of Surgery and Bucco-Maxillofacial Traumatology and Periodontology, Ribeirão Preto School of Dentistry, University of São Paulo – USP, Ribeirão Preto, SP, Brazil;2. Federal University of Ceará – UFC, Sobral, Ceará, Brazil;3. Department of Biochemistry and Molecular Biology, Federal University of Ceará – UFC, Fortaleza, Ceará, Brazil;4. Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;5. Division of Histology, Department of Basic Sciences, Dental School of Araçatuba, São Paulo State University – UNESP, Brazil |
| |
| Abstract: | N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymers containing oligopeptide side-chains terminating in anticancer drugs (daunomycin, adriamycin) have been synthesized. The bond between the drug and the carrier was stable in the bloodstream, but was cleaved intracellularly on exposure to the lysosomal cysteine proteinases. HPMA copolymers have also been modified with targeting moieties: galactosamine, which targets the conjugate to hepatocytes; anti θ antibodies recognizing θ alloantigen expressed on immunocompetent lymphocytes; and fucosylamine, since there is a receptor on mouse leukemia L1210 cells that recognizes and binds this carbohydrate moiety.In vitro and in vivo experiments demonstrated preferential interaction of modified HPMA copolymers with the respective target cells. Subsequent experiments were performed to test the pharmacological activity of anticancer polymeric prodrugs in vivo against L1210 leukemia in DBA2 mice. Two localizations of tumor were chosen — intraperitoneal and subcutaneous. In both cases experimental animals were treated intraperitoneally with free drug or drug-HPMA copolymer conjugates. HPMA copolymers containing anticancer drugs have shown therapeutic effect only when the oligopeptide sequence between the drug and the polymeric carrier was biodegradable.Polymeric products produced increased life span and an increased number of long term survivors depending on the structure of the conjugate (i.e. presence of biodegradable side-chains or targeting moieties), timing of administration and number of doses. From the data presented it can be concluded that targetable anticancer polymeric prodrugs may be useful clinically. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
