Other Types Of Coronas

In the previously reviewed literature dealing with PEG-coated drug carriers, it was emphasized that even at highest surface density and with longest PEG chains (20K), plasma protein adsorption could not be completely avoided [64] and that, even if the blood half-life was dramatically increased, the final destination of the nanoparticles was always MPS [43].

Therefore, a research trend is to develop new types of coatings as alternatives to the PEG ones, to provide the lowest interaction with plasma proteins and MPS. For example, in the case of liposomes, polysaccharides such as dextran and pullulan, and glycolipids (mainly monosialoganglioside GMj) have been proposed as possible coatings to replace PEG [112, 113]. Other synthetic polymers investigated in the case of liposomes were poly(vinyl pyrrolidone) and poly(acryl amide) (PAA) [114]. Half-clearance times were equivalent for PEG and PAA of equal molecular weight and content in the liposomes. Poly(2-methyl-2-oxazoline) and poly(2-ethyl-oxazoline) were found to be as effective as PEG in prolonging blood circulation time and in minimizing the uptake of liposomes by MPS [115].

In the case of nanoparticles, up-to-date, mainly polysac-charidic coatings were explored as candidates to replace PEG. Pioneering studies dealt with nonbiodegradable nano-spheres made of poly(methyl methacrylate) coated with dex-tran by emulsion polymerization of the acrylic monomer in the presence of dextran [116]. Stable nanospheres of 220360 nm were thus obtained. Dextran- and heparin-coated nanospheres were prepared by radical emulsion polymerization of methyl methacrylate, initiated by Cerium ions in the presence of dextran or heparin [117]. These nanospheres had a prolonged blood circulation time compared to the uncoated ones [118]. Furthermore, the presence of the dextran coating reduced the interaction with the complement system [119] and with J774A1 macrophage-like cell lines [120].

In the case of biodegradable polyester nanospheres, an original procedure was proposed to coat their surface with polysaccharides. For this, graft copolymers (dextran with pending PEG chains) were used as surfactants in the nanospheres' preparation by an emulsification and solvent evaporation technique [121]. It was supposed that during particle formation, PEG anchors in the PLGA cores. Nanospheres with a rather large diameter—higher than about 480 nm— were obtained by this method.

Dextran-coated PLA nanospheres of 150-200 nm were prepared by an oil-in-water (o/w) emulsion and evaporation technique, by using dextran grafted with phenoxy groups as emulsion stabilizers [122]. These amphiphilic copolymers are strongly anchored to the nanosphere surface, thus providing protection against interaction with proteins and ensuring particle stability in the presence of salts and during freeze-drying.

More recently, core(polyester)-corona(polysaccharide) nanospheres were directly formed without the need of additional surfactants [123]. These nanospheres, of less than 200 nm, were made by using a new type of comb-like macro-molecules, polysaccharides grafted with polyesters. Moreover, because of the presence of many reactive groups, the polysaccharidic coatings should facilitate the coupling of lig-ands, by comparison with PEG [124].

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