Polymer-Drug Conjugates
Polymer-drug conjugates are nanosized drug delivery systems, which comprise several drug molecules covalently attached to a polymeric carrier. This chapter provides an overview of this technology in the context of drug delivery. Particular emphasis is giv
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Polymer-Drug Conjugates Cristina Fante and Francesca Greco
Abstract Polymer-drug conjugates are nanosized drug delivery systems, which comprise several drug molecules covalently attached to a polymeric carrier. This chapter provides an overview of this technology in the context of drug delivery. Particular emphasis is given to different approaches and techniques used to synthesise and characterise polymer-drug conjugates. In the final part of the chapter current applications of this technology are also discussed.
7.1 7.1.1
Materials Chemistry Definition of Polymer-Drug Conjugates and General Background to This Technology
Polymer-drug conjugates are a drug delivery technology where a polymer carrier is used to improve the performance of a drug (e.g. improve drug selectivity towards the target site). Unlike other systems, such as liposomes or nanoparticles where the drug is physically entrapped within the carrier, in a polymer-drug conjugate the drug is covalently attached to the polymer via a biodegradable linker (Fig. 7.1). The concept of conjugation of a drug to a polymeric carrier was first introduced in the 70s by Helmut Ringsdorf as a strategy to enhance the selectivity, cellular uptake and solubility of a drug (Ringsdorf 1975). Since then, extensive work has been carried out which has resulted in polymer-drug conjugates reaching clinical evaluation (Vasey et al. 1999; Seymour et al. 2009, also reviewed in Duncan 2006; Canal et al. 2011).
C. Fante • F. Greco (*) Reading School of Pharmacy, University of Reading, Whiteknights, UK e-mail: [email protected] I.F. Uchegbu et al. (eds.), Fundamentals of Pharmaceutical Nanoscience, DOI 10.1007/978-1-4614-9164-4_7, © Springer Science+Business Media New York 2013
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Polymer Targeting group
Linker Drug
Polymer-Drug Conjugate
Polymeric Nanoparticle
Liposome
Polymeric Micelle
Fig. 7.1 Schematic representation of a polymer-drug conjugate and other drug delivery technologies. In polymer-drug conjugates the drug is covalently attached to the polymer via a biodegradable linker
The rationale for conjugating a drug to a polymer stems from the fact that the biological behaviour of the drug can be significantly altered by increasing its molecular weight (MW). Covalent conjugation to a polymer results in: – Prolonged circulation time of the drug. The polymer can protect the conjugated drug from premature inactivation during its delivery to the site of action; in addition, the macromolecular size of the conjugate prevents the early elimination of the drug through renal filtration. – Restricted body distribution. An intravenously administered drug is generally able to diffuse throughout the body, with no selectivity towards the target tissue. On the other hand, the macromolecular size of a conjugate prevents extravasation of the drugs in areas where the vascular endothelium is continuous. In fact, conjugation to a polymer restricts drug access to those tissues where the vasculature presents fenestrations and gaps of appropriate size (>2
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