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

Abstract

In order to study its fate in vivo, a low molecular-weight polylactide homopolymer was derivatized with a p-methoxyphenyl moiety, so as to make it susceptible to radiolabeling with 125 I . A low molecular weight polylactide–polyethyleneglycol copolymer capped with a p-methoxyphenyl residue was also synthesized. The derivatized polymers were successfully [ 125 I ]iodinated in organic medium. The radiolabeled products were freed from [ 125 I ]iodide by dialysis and shown to be stable for 24 h on incubation at 37°C in buffered saline or in blood. On longer incubation at 37°C in buffered saline the radiolabeled polylactide released [ 125 I ]iodide and [ 125 I ]iodinated 3-( p-methoxyphenyl)propionic acid. The radiolabeled copolymer was more stable on incubation at 37°C in buffered saline, but some [ 125 I ]iodide was released. The tissue distribution of radioactivity was determined 5 min, 1, 5 and 24 h after injecting male rats with 125 I -labeled homopolymer or copolymer. Intravenous, intraperitoneal and subcutaneous injection routes were employed. Further rats were injected with [ 125 I ]iodide, to aid interpretation of the data. After administration of labeled homopolymer, a high concentration of radioactivity was found in the liver tissue. The levels slowly decreased over 24 h, and the polymer was successively found in the small and large intestine and the faeces. This is probably indicative of excretion via the bile. Concurrently radioactivity was excreted in the urine. After administration of labeled copolymer, a high concentration of radioactivity was found in the liver and the residual soft tissue, the latter fraction containing two-thirds of the radioactivity one hour after injection. The precise tissue location that this result indicates was not identified. After 1 h radioactivity was excreted in the faeces, again probably via the bile, and in the urine. Tissue distributions after intraperitoneal or subcutaneous injections were concordant with the above results and interpretations, with the additional factor of slow clearance from the injection site.