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 terms of statistical behavior of macromolecules in solution, when polymer flexibility plays a key role. According to the mechanism proposed, surface-grafted chains of flexible and hydrophilic polymers form dense ''conformational clouds'' preventing other macromolecules from the interaction with the surface even at low concentration of protecting polymer. Using liposomes as an example, experimental evidence is presented of the importance of protecting polymer flexibility in liposome steric protection. Further possible applications of the suggested model are discussed. 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 requirements for protecting polymers are formulated, and differences in steric protection of liposomes and particles are discussed. The scale of protective effect is interpreted as the balance between the energy of hydrophobic anchor interaction with the liposome membrane core or with the particle surface and the energy of polymer chain free motion in solution.