POLYMERS ON THE SURFACE OF NANOCARRIERS - MODULATION OF CARRIER PROPERTIES AND BIODISTRIBUTION

Physico-chemical and biological properties (including biodistribution) of nanoparticulate drug carriers (polymeric nanoparticles, liposomes, latex particles, micelles, etc.) can be modified in a desirable fashi on by grafting various polymers to the carrier surface. The most vivid example of such modification is the preparation of longcirculating li posomes by coating them with polyethylene glycol (PEG). The mechanism of PEG protective action is described in terms of polymer properties i n solution. It includes the formation of impermeable ''conformational cloud'' of PEG over the liposome surface, which prevents liposome inte raction with other substances from the surrounding medium. Fluorescenc e quenching experiments as well as computer simulation confirm the imp ortance of polymer chain flexibility for steric protection effect. Fle xible synthetic polymers other than PEG (such as polyacrylamide or pol yvinylpyrrolidone) can also serve as steric protectors for nanocarrier s. The optimization of carrier (liposome) modification in respect of p olymer-to-carrier ratio permits to find conditions where some other fu nctional moieties might be grafted onto carrier surface together with protecting polymer. Using this approach sterically protected long-circ ulating immunotargeted carriers (liposomes) have been prepared, which demonstrated good combination of longevity and targetability in vivo. Surface coating with PEG was also proved to be effective in steric sta bilization of polymeric biodegradable nano-carriers for drugs and diag nostic agents, as well as for nondegradable latex particles. Surface g rafting of nanocarriers with certain polymers can influence their spec tral properties. Thus, the contrast properties of Gd-containing liposo mes used for experimental MR imaging (for example, lymph nodes imaging ) might be improved by simultaneous incorporation of Gd-containing che late and PEG into the liposomal membrane. Generally speaking, surface modification with different polymers is a powerful tool for designing nanocarriers with desired properties.