In 1975 Prof. H. Ringsdorf proposed a model for rational design of polymeric prodrugs [J. Polym. Sci. Symp. 51 (1975) 135]. The model has been the most important basis for research in the field, since it was the first model that took into account both the chemical and biological aspects needed for the design of polymeric prodrugs. This paper deals with the most important properties that were discovered by designing polymeric prodrugs: prolongation of action of the drug, controlled release of the drug, passive tumor accumulation by the EPR-effect and alteration of body distribution and cell uptake. Over the years, other objectives have been formulated and other properties of polymer-drug conjugates were discovered. One recent example, the immunoprotective ability of polymeric prodrugs, is described in more detail in this paper.

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Dendritic poly-[N-(2-hydroxyethyl)-L-glutamine] (PHEG) with different molecular weights were synthesized by aminolysis of dendritic poly-(γ-benzyl-L-glutamate) (PBG), which was obtained by polymerization of the corresponding N-carboxyanhydride (NCA) with poly(amido amine) (PAMAM, starburst ® ) of the fourth generation as initiator. Dynamic light scattering (DLS) was used to determine the size of the polymeric carriers and to compare the dendritic polymer to the linear analogue. The body distribution and blood clearance of 125 I-radiolabelled linear and dendritic PHEG with similar molecular weight were investigated in female BALB/c mice.

Invertase from Saccharomyces cerevisiae was activated by periodate treatment and further reacted with ethylenediamine/sodium borohydride. Carboxymethylcellulose was then attached to ethylenediamine-modified invertase using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as coupling agent. The modified enzyme contained 3.5 mol of polysaccharide per mol of holoenzyme, and retained about 56% of the initial invertase activity. The thermostability of invertase increased from 64 to 70° C, the thermal inactivation at different temperatures ranging from 60 to 70° C was markedly reduced for polymer-modified enzyme. An increase of 9.1 kJ mol−1 in activation free energy of inactivation was determined for invertase after modification. Functional stability was increased for carboxymethylcellulose-invertase complex in the range of pH between 2.0 and 12.0. The conjugate was also more resistant to denaturation by 6 M urea solution.