POLYMER-COATED LONG-CIRCULATING MICROPARTICULATE PHARMACEUTICALS

The field of long-circulating microparticulate drug carriers is review ed. The protective effect of certain polymers including poly(ethylene glycol) on nanoparticulate carriers (liposomes, nanoparticles, micelle s) is considered in terms of statistical behaviour of macromolecules i n solution. Using liposomes as an example, the mechanism is discussed assuming that surface-grafted chains of flexible and hydrophilic polym ers form dense 'conformational clouds' preventing other macromolecules from interaction with the surface even at low concentrations of the p rotecting polymer. The scale of the protective effect is interpreted a s the balance between the energy of the hydrophobic anchor interaction with the liposome membrane core or with the particle surface and the energy of the polymer chain free motion in solution. The possibility o f using protecting polymers other than poly(ethylene glycol) is analys ed, and examples of such polymers are given, based on polymer-coated l iposome biodistribution data. General requirements for protecting poly mers are formulated. Sterically protected nanoparticles and micelles a re considered, and differences in steric protection of liposomes and p articles are discussed. The problem of the preparation of drug carrier s combining longevity and targetability is analysed. The biological co nsequences of steric protection of drug carriers with surface-grafted polymers are discussed, and possible clinical applications for long-ci rculating pharmaceutical carriers are considered.