Hydroxyethyl starch (HES) is a water soluble semisynthetic polysaccharide that is used as a plasma volume expander and cryoprotectant. In order to produce a fully biodegradable amphiphilic polymer, HES was esterified with lauric, palmitic, and stearic acids under mild reaction conditions using dicyclohexyl carbodiimide (DCC) and dimethylaminopyridine (DMAP). The molar substitution of the acyl chains (MSfatty acid) was determined with 1H NMR spectroscopy, while the conformational state of the hydrocarbon chains in the graft copolymer was determined using Raman spectroscopy. Furthermore, the aqueous self-assembly of the modified polymer was studied using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Results show the formation of 20 to 30 nm micelles, and 250 to 350 nm polymeric vesicles. Electron spin resonance (ESR) spectroscopy was used to study the microenvironment of a hydrophobic spin probe loaded inside the formed nanodispersion. It was possible to identify the location of the probe and its distribution between the micelles and vesicles. Finally, the hydrophobically modified HES might find use as a potential drug carrier, warranting the future investigation of its ability to encapsulate and deliver drug candidates.

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Some Pluronics, particularly F127, are known to stabilize nanospheres and prolong their circulation time in vivo. However, these copolymers of poly(ethylene glycol) (PEG) and poly(propylene glycol) are not biodegradable, and despite the long history, there is no approved commercial product using F127 for parenteral administration until now. Meanwhile, hydroxyethyl starch (HES) is a biodegradable polymer that is currently investigated as a substitute for PEG. In order to produce a fully biodegradable amphiphilic polymer, we esterified different molar masses of HES with lauric acid to get different molar substitutions. These polymers, as well as Pluronic F68 and F127, were used to stabilize poly(lactic-co-glycolic acid) (PLGA) nanospheres prepared by nanoprecipitation. For physicochemical characterization, the particle size, zeta potential, and the thickness of the adsorbed polymer layer were measured. The ability of the polymer coating to prevent the adsorption of human serum albumin (HSA) and fibrinogen (FBG) was evaluated. Finally, the phagocytosis of the stabilized nanospheres by a monocyte macrophage cell line (J774.2) was assessed. Results show that the PLGA nanospheres had an average particle size of 110-140 nm. The thickness of the adsorbed polymer layer increases with the increase in molar mass, and is generally higher for HES laurates than the studied Pluronics. Pluronic F68, F127 as well as the HES laurates with low molar substitution prevented the adsorption of HSA. HES laurates with low molar substitution and F127, but not F68, prevented the adsorption of FBG. The phagocytosis experiments showed that the HES laurates, particularly the one with the highest molar mass, could reduce the uptake of the nanospheres better than F68 and comparable to F127. Finally, these results warrant in vivo experiments to evaluate how the HES laurates can affect the pharmacokinetics and fate of the nanospheres.