ABSTRACT
The treatment of human diseases such as cancer, inammatory disorders, or degenerative disorders is challenging because these pathologies involve the dysregulation of endogenous and often essential cellular processes. Human diseases are generally heterogeneous entities; not all cells present with the same distorted phenotype and/or genotype. In addition, several different cell types are involved in diseased tissues: the diseased cells, the normal cell populations from which the disease evolved, vascular cells, broblasts, and immune cells. As a consequence, there is a need to protect the normal cells of the diseased tissue, as well as other tissues and organs from the toxicity of therapeutic agents. Most therapeutic drugs distribute to the whole body, which results in the general toxicity and poor acceptance of the treatment by patients. The targeted delivery of chemotherapeutics to dened cells, for example, either stromal or cancer cells in cancer lesions, dened inammatory cells in immunological disorders, or macrophages in degeneration or atheromatosis, is one of the main challenges and is a very active eld of research in the development of treatment strategies to enhance the efcacy and minimize the side effects of drugs. Disease-associated cells express molecules that are different or differently expressed than their normal counterparts. Therefore, one goal in the eld of targeted therapies is to develop chemically derivatized drug vectors that are able to target dened
18.1 Introduction .......................................................................................................................... 481 18.2 Principles and Background for Drug Delivery Using Polymeric Drug Conjugates ............. 482
18.2.1 Biological Issues and Strategies for Targeted Drug Delivery ................................... 482 18.2.2 Characteristics of Polymeric Drug Delivery Systems in Human Diseases ..............484 18.2.3 Drug-Polymer Conjugate Nanoparticles ..................................................................485 18.2.4 Nanoparticles for Human Therapy ...........................................................................486 18.2.5 Polymer Drug Conjugate Delivery Systems ............................................................. 489 18.2.6 Polymer Functionalization ........................................................................................490 18.2.7 Linkers ...................................................................................................................... 493 18.2.8 Toxicity Issues and Biocompatibility Considerations ............................................... 494
18.3 Drug Conjugation to Polymers for Efcient and Selective Drug Release and Delivery: A Few Examples ............................................................................................ 495 18.3.1 Denition of the Optimized Characteristics of Drug-Polymer Conjugates
for Therapy ............................................................................................................... 495 18.3.2 Anticancer Drug-Delivery Systems .......................................................................... 497 18.3.3 Transport across the BBB ......................................................................................... 499 18.3.4 Imaging Agents for Cancer or the Atheromatous Plaques and
Drug-Delivery Systems ............................................................................................. 501 18.4 Concluding Remarks ............................................................................................................502 Acknowledgment ...........................................................................................................................505 References ......................................................................................................................................505
