Biodegradation of and tissue reaction to 50:50 poly(DL‐lactide‐co‐glycolide) microcapsules

Abstract

The biodegradation of the copolymer 50:50 poly(DL-lactide-co-glycolide)-lypressin microcapsules was studied by light and electron microscopic methods and 14C release. Intramuscular injection sites of microcapsules in rats were studied by dissecting and conventional light microscopy as well as scanning (SEM) and transmission electron microscopy. A minimal localized acute myositis was seen initially at the injection sites. By Day 4, a few small foreign body giant cells were present participating in the minimal foreign body response. Later the inflammatory cells decreased and the individual microcapsules were walled off by immature fibrous connective tissue and large syncytial foreign body giant cells. By Day 35, definitive changes in some microcapsules, consisting of a granular and slightly eroded appearance of the internal matrix, were seen by SEM. By Day 42, the outer rims of the microcapsules were extensively eroded. At Day 56, the inflammatory and connective tissue reactions were almost completely resolved and biodegradation continued so that only remnant pieces of the microcapsules were present at Day 63. The morphologic picture correlated well with loss of 14C radioactivity, which could no longer be detected at the injection sites on Day 56. Phagocytosis did not seem to be an important factor in the biodegradation.

In vitro elution of ofloxacin from a bioabsorbable polymer

“…In our study, the 5050 DLlactide/glycolide copolymer had the fastest degradation rate among the polymer materials used, since negligible concentrations could be determined in the elution fluid after 46 days. In contrast, the 85: 15 DLlactide/glycolide polymer composites appear to elute drug for approximately 150 days, a value quite similar to that which has been previously observed in vivo (Visscher et al 1985). Our study suggests that both the volume ratio of po1ymer:ofloxacin and the ratio of 1actide:glycolide can alter the release characteristics of the incorporated antimicrobial.…”

“…Recently, several investigators have reported on the development and use of biodegradable and bioabsorbable antibiotic composites (Ikada et al 1985, Visscher et al 1985, Wei et al 1991. We selected ofloxacin for our study because of its broad spectrum of antimicrobial activity for both Gram-positive and Gram-negative bacteria.…”

How to achieve sustained and complete protein release from PLGA-based microparticles?

“…Polymers derived from D,L lactic and glycolic acids, poly(lactide-co-glycolide) (PLGA), are biocompatible and biodegradable (Visscher et al, 1985;Fournier et al, 2003), they have been widely employed with this aim in mind. Drug release from these systems is due to drug diffusion through water-filled networks of pores and channels coupled with the bulk erosion of the microspheres by hydrolysis of the polymer's ester bond linkages.…”

Efficacy of Rifabutin-Loaded Microspheres for Treatment ofMycobacterium Avium-Infected Macrophages and Mice

“…A common formulation used in studies for mycobacterial therapy involved the thermoplastic aliphatic poly(esters) such as the copolymer of lactide and glycolide, poly(lactide-co-glycolide) (PLGA) (Jain 2000). This particular formulation is based upon one originally used to make synthetic resorbable sutures (Gilding and Reed 1979) and is known to be biocompatible in humans, as well as the metabolic byproducts, lactic acid and glycolic acid (Visscher et al 1985(Visscher et al , 1986Visscher, Robison, and Argentieri 1987). Degradation of PLGA is by means of a nonenzymatic reaction (Tice and Cowsar 1984;Wu 1995).…”