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Three different models were applied to study the reproduction, survival and dispersal of Mnemiopsis leidyi in the Scheldt estuaries and the southern North Sea: a high-resolution particle tracking model with passive particles, a low-resolution particle tracking model with a reproduction model coupled to a biogeochemical model, and a dynamic energy budget (DEB) model. The results of the models, each with its strengths and weaknesses, suggest the following conceptual situation: (i) the estuaries possess enough retention capability to keep an overwintering population, and enough exchange with coastal waters of the North Sea to seed offshore populations; (ii) M. leidyi can survive in the North Sea, and be transported over considerable distances, thus facilitating connectivity between coastal embayments; (iii) under current climatic conditions, M. leidyi may not be able to reproduce in large numbers in coastal and offshore waters of the North Sea, but this may change with global warming; however, this result is subject to substantial uncertainty. Further quantitative observational work is needed on the effects of temperature, salinity and food availability on reproduction and on mortality at different life stages to improve models such as used here.

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.

PEG-grafted dextran and PHEG derivatives were synthetized to be used as drug carriers. The PEG-containing copolymers showed potential tensioactive properties. Dynamic light-scattering measurements and surface tension measurements indicated that phase separation of dextran/PHEG and PEG occurs on a molecular level in the conjugates and results in the formation of aggregates with a PEG core in which free PEG can be trapped. Blood clearance and body distribution studies were performed on female BALB/c mice. PEG-modified polymers with a high hydrodynamic volume stay longer in the blood stream compared with the non-modified polymers. These high molecular weight conjugates stay in the blood for several hours. Conjugates with a molecular weight below the renal threshold barrier are cleared much faster from the blood and excreted from the body. Concerning the body distribution, the PEG conjugates are not excreted very fast and are not taken up by any organ in particular. It is notable that PEG substitution prevents dextran from liver uptake. Furthermore, a method was developed to link an oligopeptide spacer-drug model and PEG to the same polymer. It was shown that PEG substitution has only little influence on the enzymatic release of the model drug. The above-mentioned results showed that the PEG-grafted polymers were promising candidates for drug carriers.

Poly(ethylene glycol)-dextran (PEG-DEX) conjugates have been used as a combined stabilizer and surface modifier to produce resorbable poly(DL-lactide-co-glycolide) (PLG) microparticles by an emulsification/solvent evaporation technique. The use of PEG or dextran polymers alone was incapable of producing microparticles. Particle size measurements revealed smaller mean particle sizes (480 nm) and improved polydispersity when using a 1.2% PEG substituted conjugate relative to a 9% substituted material (680 nm). PLG microparticles modified by post-adsorbed PEG-DEX conjugates flocculated in 0.01 M salt solutions, whereas PLG microparticles prepared using PEG-DEX as a surfactant were stable in at least 0.5 M NaCl solutions. Surface modification of PLG microparticles was confirmed by zeta potential measurements and surface analysis using X-ray photoelectron spectroscopy. The presence of surface exposed dextran was confirmed by an immunological detection method using a dextran-specific antiserum in an enzyme-linked immunosorbent assay. The findings support a model in which the PEG component of the PEG-DEX conjugate provides an anchor to the microparticle surface while the dextran component extends from the particle surface to contribute a steric stabilization function. This approach offers opportunities for attaching hydrophilic species such as targeting moieties to biodegradable microparticles to improve the interaction of drug carriers and vaccines with specific tissue sites.