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

Abstract

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.

Materials in particulate form for tissue engineering. 1. Basic concepts

“…These particular traits render these systems very interesting for drug delivery applications. Furthermore, tuning of the biodegradability can be performed by blending PLA and PGA in a co-polymer (PLGA), and by changing the proportion of each of these materials in the copolymer (Miller et al, 1977;Pillai and Panchagnula, 2001;Grayson et al, 2004), as PLA degrades much slower than PGA. Degradation of PLA and PLGA is known to proceed by hydrolytic scission of the polymer chain and depolymerization is influenced by molecular weight (MW), polydispersity and crystallinity (Weinhold et al, 1998;Li and Wozney, 2001).…”

Drug delivery systems in urology—getting “smarter”

“…4). 45,46 The active format (Fig. 3) is constructed from a silicon wafer containing multiple microscale reservoirs that can be opened to release drugs through electrochemical dissolution of a thin gold membrane (anode) which covers the micro-reservoirs.…”

Polymer Biocompatibility

“…Mild inflammatory reactions have been observed after a massive release of acidic degradation in vivo depending on the amount and degradation rate of the material (Bostman et al, 1990;Grayson et al, 2004;Holy et al, 1999;Hutmacher, 2000;Thomson et al, 1999;Young et al, 2002). However, the use of synthetic biocompatible material has the enormous advantage of reproducible synthesis and the mechanical and chemical properties including the structure, size, viscosity, and porosity, as well as degradation rate of the desired scaffold can be controlled.…”