Radiolabeling, stability, and body distribution in rats, of low molecular weight polylactide homopolymer and polylactide-polyethyleneglycol copolymer

In order to study its fate in vivo, a low molecular-weight polylactide homo polymer was derivatized with ap-methoxyphenyl moiety, so as to make it susc eptible to radiolabeling with I-125. A low molecular weight polylactide-pol yethyleneglycol copolymer capped with a p-methoxyphenyl residue was also sy nthesized. The derivatized polymers were successfully [I-125]iodinated in o rganic medium. The radiolabeled products were freed from [I-125]iodide by d ialysis and shown to be stable for 24 h on incubation at 37 degrees C in bu ffered saline or in blood On longer incubation at 37 degrees C in buffered saline the radiolabeled polylactide released [I-125]iodide and [I-125]iodin ated 3-(p-methoxyphenyl)propionic acid. The radiolabeled copolymer was more stable on incubation at 37 degrees C in buffered saline, but some [I-125]i odide was released. The tissue distribution of radioactivity was determined 5 min, 1, 5 and 24 h after injecting male rats with I-125-labeled homopoly mer or copolymer. Intravenous, intraperitoneal and subcutaneous injection r outes were employed. Further rats were injected with [I-125]iodide, aid int erpretation of the data. After administration of labeled homopolymer, a hig h concentration of radioactivity was found in the liver tissue. The levels slowly decreased over 24 h, and the polymer was successively found in the s mall and large intestine and the faeces. This is probably indicative of exc retion via the bile. Concurrently radioactivity was excreted in the urine. After administration of labeled copolymer, a high concentration of radioact ivity was found in the liver and the residual soft tissue, the latter fract ion containing two-thirds of the radioactivity one hour after injection. Th e precise tissue location that this result indicates was not identified. Af ter 1 h radioactivity was excreted in the faeces, again probably via the bi le, and in the urine. Tissue distributions after intraperitoneal or subcuta neous injections were concordant with the above results and interpretations , with the additional factor of slow clearance from the injection site. (C) 1999 Elsevier Science Ltd. All rights reserved.