Synthesis and Micellization of Linear−Dendritic Copolymers and Their Solubilization Ability for Poorly Water-Soluble Drugs

Abstract

A series of linear-dendritic copolymers were synthesized by conjugating BE block copolymers (B8E41 and B16E42, B=1,2-butylene oxide and E=ethylene oxide) with G1-3 PAMAM dendrimers via carbamate bonds. The critical micelle concentrations of the dendrimer conjugates were less than
0.11 mmol dm-3. Light scattering measurements indicated that “flowerlike” micelles were formed when two B chains from each conjugate entered the micelle core. Further association of the micelles was found for the conjugates containing more than two BE chains per dendrimer. Drug solubilization in micellar solutions of the conjugates was mainly by the incorporation of drug molecules in micelle cores, with marginal enhancement of solubility attributable to encapsulation in the dendritic micelle coronas. The solubility of hydrophobic drugs in 1 wt%micellar solutions was increased up to 6-fold. Solubilization of ionic drugs was unfavorable due to the limited penetration of ionized drug molecules into the micelle cores.