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 PNU1 66945, a conjugate between a synthetic polymeric drug-carrier poly[N-( (2-hydroxypropyl)-methacrylamide)] (PHPMA) and the antitumor drug Pacl itaxel. Thirteen fractions of the conjugate PNU and six fractions of t he polymeric drug-carrier PHPMA were prepared and characterized by siz e-exclusion chromatography, viscometry, and light scattering. The mola r 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) w ere determined. A Stockmayer-Fixman plot was utilized to derive the un perturbed dimensions of the macromolecules. The presence of the drug c onsiderably influences the conformation of the macromolecules. For PHP MA and PNU, respectively, the slopes of the power law [eta] = f(M) wer e 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.