Hydrotropic dendrimers of generations 4 and 5: synthesis, characterization, and hydrotropic solubilization of paclitaxel.

Polyglycerol dendrimers (PGDs) with 4-5 generations were synthesized and used to investigate the effect of dendritic architecture and its generation on aqueous solubilization of paclitaxel (PTX), a poorly water-soluble drug. Chemical and physical properties of the PGDs were characterized by NMR, MALDI-TOF mass, GPC, viscosity, and dynamic light scattering measurements. The PTX solubility in all the solutions of PGDs, even below 10 wt %, was much higher than that in PEG400 that is commonly used as a cosolvent or a hydrotropic agent. Increase in the PTX solubility by PGDs was dependent on the dendrimer generation. The dendritic structure was the reason for the enhanced solubility of PTX even at low concentrations. (1)H NMR spectra of PTX before and after mixing with PGDs in D(2)O suggested that the aromatic rings and some methyne groups of PTX were surrounded by PGDs. PGDs, which do not require hydrophobic segment as in polymeric micelles, provide an alternative method of hydrotropic solubilization of poorly soluble drugs.