Differential degradation rates in vivo and in vitro of biocompatible poly(lactic acid) and poly(glycolic acid) homo- and co-polymers for a polymeric drug-delivery microchip.
The biocompatibility and biodegradation rate of component materials are critical when designing a drug-delivery device. The degradation products and rate of degradation may play important roles in determining the local cellular response to the implanted material. In this study, we investigated the biocompatibility and relative biodegradation rates of PLA, PGA and two poly(lactic-co-glycolic acid) (PLGA) polymers of 50:50 mol ratio, thin-film component materials of a drug-delivery microchip developed in our laboratory. The in vivo biocompatibility and both in vivo and in vitro degradation of these materials were characterized using several techniques. Total leukocyte concentration measurements showed normal acute and chronic inflammatory responses to the PGA and low-molecular-weight PLGA that resolved by 21 days, while the normal inflammatory responses to the PLA and high-molecular-weight PLGA were resolved but at slower rates up to 21 days. These results were paralleled by thickness measurements of fibrous capsules surrounding the implants, which showed greater maturation of the capsules for the more rapidly degrading materials after 21 days, but less mature capsules of sustained thicknesses for the PLA and high-molecular-weight PLGA up to 49 days. Gel-permeation chromatography of residual polymer samples confirmed classification of the materials as rapidly or slowly degrading. These materials showed thinner fibrous capsules than have been reported for other materials by our laboratory and have suitable biocompatibility and biodegradation rates for an implantable drug-delivery device.
Grayson
Amy C R
AC
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Voskerician
Gabriela
G
Lynn
Aaron
A
Anderson
James M
JM
Cima
Michael J
MJ
Langer
Robert
R
D001672:Biocompatible Materials; D002845:Chromatography; D002850:Chromatography, Gel; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006016:Glycolates / Q000737:chemistry; D007249:Inflammation; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D007962:Leukocytes / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D020411:Oligonucleotide Array Sequence Analysis; D011091:Polyesters; D011093:Polyethylene Terephthalates / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties; D013997:Time Factors
D001672:Biocompatible Materials; D004337:Drug Carriers; D006016:Glycolates; D011091:Polyesters; D011093:Polyethylene Terephthalates; D011108:Polymers; C031149:glycolic acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C025539:Lavsan; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)