Dilute-solution properties of a polymeric antitumor drug carrier by size-exclusion chromatography, viscometry, and light scattering

An investigation is reported on the dilute-solution properties of PNU166945, a conjugate between a synthetic polymeric drug-carrier poly[N-((2-hydroxypropyl)-methacrylamide)] (PHPMA) and the antitumor drug Paclitaxel. Thirteen fractions of the conjugate PNU and six fractions of the polymeric drug-carrier PHPMA were prepared and characterized by size-exclusion chromatography, viscometry, and light scattering. The molar mass distribution, intrinsic viscosity [eta], and dimensions [s(2)](1/2) of each fraction were determined. From M, [eta], and [s(2)](1/2), the constants of the power laws [eta] = f(M) and [s(2)](1/2) = f(M) were determined. A Stockmayer-Fixman plot was utilized to derive the unperturbed dimensions of the macromolecules. The presence of the drug considerably influences the conformation of the macromolecules. For PHPMA and PNU, respectively, the slopes of the power law [eta] = f(M) were 0.69 and 0.617, the slopes of the power law [s(2)](1/2) = f(M) were 0.55 and 0.48, and the Kuhn statistical segments were 1.7 and 2.1 nm. To our knowledge, this is the first time that an exhaustive molecular characterization of a conjugated polymeric system has been presented. (C) 1998 John Wiley & Sons, Inc.