Pharmacokinetics and distribution of 125I-PLA-b-PEO block copolymers in rats.

The PLA-b-PEO block copolymers were studied as potential carriers for anti-inflammatory and anticancer drugs. The copolymers were labeled with 125I, and their micelles in physiological saline were prepared by dialysis. Copolymer 1, with Mw = 12,360 (PLA/PEO = 7000/5000), formed particles of about 300 nm in diameter (Rh was 150 nm), whereas copolymer 2, with Mw = 20,470 (6000/14,000), made up micelles of about 72 nm in diameter (Rh was 35.8 nm). Their pharmacokinetic and biodistribution profiles were compared in normal rats and rats with carrageenan-induced inflammation after intravenous application of about 5 mg/kg of each copolymer. Copolymer 2, forming smaller particles, showed longer distribution and elimination half-lives. Both copolymers under study exhibited significantly higher uptake by inflammatory tissue compared with noninflammatory one. The study indicates that PLA-b-PEO copolymers, having different molecular weight of the chains, have similar biological behavior in most organs and tissues. Differences in the uptake by some organs (mainly kidney and bowels) and in activity level in blood at later time intervals were found. Significantly different clearance values are due to different ratios of hydrophobic and hydrophilic chains of the copolymers.