WHICH POLYMERS CAN MAKE NANOPARTICULATE DRUG CARRIERS LONG-CIRCULATING

The protective effect of poly(ethylene glycol) and some other polymers on nanoparticulate carriers including liposomes is considered in term s of statistical behavior of macromolecules in solution, when polymer flexibility plays a key role. According to the mechanism proposed, sur face-grafted chains of flexible and hydrophilic polymers form dense '' conformational clouds'' preventing other macromolecules from the inter action with the surface even at low concentration of protecting polyme r. Using liposomes as an example, experimental evidence is presented o f the importance of protecting polymer flexibility in liposome steric protection. Further possible applications of the suggested model are d iscussed. The possibility of using protecting polymers other than poly (ethylene glycol) is analyzed, and examples of such polymers are given based on polymer-coated liposome biodistribution data. General requir ements for protecting polymers are formulated, and differences in ster ic protection of liposomes and particles are discussed. The scale of p rotective effect is interpreted as the balance between the energy of h ydrophobic anchor interaction with the liposome membrane core or with the particle surface and the energy of polymer chain free motion in so lution.