Synthetic macromolecular drug carriers: biodistribution of poly[(N-2-hydroxypropyl)methacrylamide] copolymers and their accumulation in solid rat tumors.

摘要: To optimize polymer design for tumor directed drug delivery, the fate and total body distribution of soluble synthetic macromolecules, derived from copolymers [(N-2-(hydroxypropyl)methacrylamide] (HPMA) were monitored scintigraphically after radiolabeling with 131I during a seven day time window. Equimolar concentrations radioiodinated HPMA small amounts methacryloyltyrosinamide (pHPMA) differing in molecular weight (23.4 kD, 27.3 30.5 44 58.4 60.1 kD) injected intravenously into Copenhagen rats bearing Dunning prostate carcinomas (subline R3327-AT1). Scintigraphic data validated by determining absolute [131I]pHPMA both tissue normal organs sacrificing animals. Copolymers cleared blood circulation molecular-weight dependent manner, either via excretion or extravasation neoplastic tissues. While patterns pHPMAs quite similar, copolymer uptake differed. The higher weight, more radioactivity was taken up organs. Highest seen lung, liver, spleen. In solid tumors, kinetics pHPMA accumulation clearly on weight. below renal threshold peaked at 24 hours p.i. then remained constant. contrast, above clearance displayed continuous reaching significantly uptake, presumably due to very non existent release tissue. Absolute determined dissection analysis 0.5 ± 0.1% dose/g kD 1.2 pHPMA, respectively. conclusion, our results demonstrate influence plasma time, organ clearance. are all tissues except spleen effectively, these polymers accumulate tumors size well known “enhanced permeability retention” (EPR) effect. These fundamental interest ongoing studies pharmacokinetics polymers, especially when molecules conjugated targeting moieties therapeutic diagnostic agents