No abstract

The results of a comparative study of hyperbranched, partially esterified polyglycerols with their linear polyglycerol analogues with respect to molecular encapsulation and phase transfer are reported. Two hyperbranched polyglycerol samples with molecular weights of 3000 and 8000 g/mol (Mw/Mn = 1.3), respectively, have been partially esterified using palmitoyl chloride. The same modification was applied to the structurally analogous linear polyglycerol (3000 g/mol). A detailed UV-vis study correlated with viscosity experiments demonstrated that only the hyperbranched core-shell structures form "nanocapsules", leading to the encapsulation of polar guest molecules. The results underline the crucial role of the hyperbranched topology and the resulting solution conformation for supramolecular guest encapsulation and phase transfer. The unusually compact ("collapsed") structure assumed by the hyperbranched core-shell amphiphiles in apolar media is responsible for the formation of a hydrophilic compartment, capable of irreversibly taking up guest molecules.

A simple and efficient concept has been developed for the synthesis of pH‐responsive molecular nanocarriers based on commercially available hyperbranched polymers. These dendritic core‐shell architectures can encapsulate, transport, and selectively release polar guest molecules in an acidic environment (pH 3–6, see scheme). The observed release properties render these molecular nanocarriers promising candidates for controlled drug and gene delivery.

Nonionic amphiphiles and particularly block copolymers of ethylene oxide and propylene oxide (Pluronics) cause pronounced chemosensitization of tumor cells that exhibit multiple resistance to antineoplastic drugs. This effect is due to inhibition of P-glycoprotein (P-gp) responsible for drug efflux. It was suggested that the inhibition of P-gp might be due to changes in its lipid surrounding. Indeed, high dependence of P-gp activity on the membrane microviscosity was demonstrated [Regev et al. (1999) Eur. J. Biochem. 259, 18−24], suggesting that the ability of Pluronics to affect the P-gp activity is mediated by their effect on the membrane structure. We have found recently that adsorption of Pluronics on lipid bilayers induced considerable disturbance of the lipid packing [Krylova et al. (2003) Chemistry 9, 3930−3936]. In the present paper, we studied 19 amphiphilic copolymers, including newly synthesized hyperbranched polyglycerols, Pluronic and Brij surfactants, for their ability to accelerate flip-flop and permeation of antitumor drug doxorubicin (DOX) in liposomes. It was found that not only bulk hydrophobicity but also the chemical microstructure of the copolymer determines its membrane disturbing ability. Copolymers containing polypropylene oxide caused higher acceleration of flip-flop and DOX permeation than polysurfactants containing aliphatic chains. The effects of copolymers containing hyperbranched polyglycerol “corona” were more pronounced, as compared to the copolymers with linear poly(ethylene oxide) chains, indicating that a bulky hydrophilic block induces additional disturbances in the lipid bilayer. A good correlation between the copolymer flippase activity and a linear combination of copolymer bulk hydrophobicity and the van der Waals volume of its hydrophobic block was found. The relationship between the structure of a copolymer and its ability to disturb lipid membranes presented in this paper may be useful for the design of novel amphiphilic copolymers capable of affecting the activity of membrane transporters in living cells.