Their History and Characteristics

In recent decades, the use of polymers as carriers of both covalently bound and physically entrapped drugs has been widely explored. The larger hydrodynamic volume of polymers contributes to the

FIGURE 4.1 Typical nanocarriers.

increase in the plasma half-life of drug-polymer conjugates, increasing the probability of accumulation of the therapeutic agent in the tumor tissue because of the EPR effect. Drug-polymer conjugates (Figure 4.1) exhibit improved water solubility and reduced toxicity as a result of accumulation in the target tissue, and they protect the drug from enzymatic degradation or hydrolysis. However, drugs covalently bound to a polymer lose their pharmacological activity because a drug cannot interact with the target site because of steric constraints. In this respect, in 1975, Ringesdorf11 was the first to propose a model for the rational design of a polymer conjugate with a drug that consisted of five components: the polymeric backbone, the drug, the spacer, the targeting group, and the solubilizing agent. The polymeric carrier can be either an inert or a biodegradable polymer. The drug can be fixed directly or via a spacer group onto the polymer backbone that is about 5-40 kDa. The proper selection of this spacer offers the possibility of controlling the site and the rate of release of the active drug from the conjugate by hydrolytic or enzymatic cleavage.

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