In vivo and in vitro elimination of aliphatic polyanhydrides.
The hydrolysis and elimination processes of biopolyanhydrides has been studied using a polymer series of linear aliphatic diacids. This polymer series degrade into their monomer counterparts at about the same rate but differ in the water solubility of their degradation products. Polymers based on natural diacids of the general structure -[OOC-(CH2)x-CO]n- where x is between 4 and 12 were implanted subcutaneously in rats and the elimination of the polymers from the implantation site was observed. The in vitro hydrolysis of this polymer series was studied by monitoring the weight loss, release of monomer degradation products and the content of anhydride bonds in the polymer as a function of time. A dependence was found between the monomer solubility and the rate of polymer elimination in both in vivo and in vitro. The elimination time for polymers based on soluble monomers (x = 4-8) was 7-14 days, while the polymers based on low monomer solubility (x = 10-12) were eliminated only after 8 weeks. The in vitro degradation of polyanhydrides in the presence of several common hydrolytic enzymes found around implants did not affect polymer degradation. All polymers were biocompatible and found to be useful as carriers for drug delivery.
Domb
A J
AJ
Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Nudelman
R
R
D000812:Anhydrides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001673:Biodegradation, Environmental; D002264:Carboxylic Acids / Q000378:metabolism*; D002417:Cattle; D002850:Chromatography, Gel; D016503:Drug Delivery Systems / Q000592:standards; D004798:Enzymes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D008970:Molecular Weight; D011108:Polymers / Q000378:metabolism; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared; D013696:Temperature
D000812:Anhydrides; D001672:Biocompatible Materials; D002264:Carboxylic Acids; D004798:Enzymes; D011108:Polymers