Body distribution of poly(D,L-lactide-co-glycolide) copolymer degradation products in rats.
Poly (D,L-lactide-co-glycolide) (PLGA) copolymers are among the few synthetic polymers approved for human use, but the biocompatibility of PLGA-derived oligomers and particles remains questionable. Here, high molecular weight PLGA (Mw=32,000) was radiolabeled with (125)I in chloroform solution, and the body distribution of PLGA copolymer degradation products was examined following subcutaneous implantation of round (125)I-PLGA films on the back of Sprague Dawley rats. Autoradiographic images of the PLGA implant taken at 2, 4, 6, 8, 10, and 12 weeks revealed that the central portion of the film degraded much more rapidly than the marginal portions. Examination of the body compartment distribution at these time points revealed that over one-half of the radioactivity was recovered from skin. The remaining radioactivity was concentrated in the blood, liver, and kidneys. Radioactivity steadily appeared in the blood and remained elevated up to 12 weeks after implantation, while the liver to kidney distribution began to decrease after 6 weeks. Cumulatively, these results indicate that the clearance of degraded particles and fragments from the implantation site is extremely delayed. Moreover, the degraded particles and fragments were selectively concentrated in the liver and kidneys, following release of degraded products into the bloodstream from the implantation site.
Hua
Nan
N
Shanghai Biomaterial Research and Test Center, Ninth People's Hospital, Shanghai Jiaotong University, No. 716, Xietu Road, Shanghai 200023, China.
Sun
Jiao
J
D000818:Animals; D001345:Autoradiography; D001672:Biocompatible Materials / Q000378:metabolism* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D011100:Polyglycolic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution / Q000502:physiology
D001672:Biocompatible Materials; D007457:Iodine Radioisotopes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid