Tissue Response to Biodegradable Injectable Microcapsules

Abstract

Biodegradable microcapsules have been shown to be capable of delivering a sustained release of various medicinal agents. We have observed an initial minimal, sharply localized, acute inflammatory response to intramuscularly injected microcapsules produced from various polymers. Evaluation of later time points has shown a diminishing macrophage, foreign body giant cell, and connective tissue response along with actual microcapsule degradation. No fibrous capsule formation was seen. Complete resolution of the tissue reaction can be expected, with the time frame depending upon the polymer utilized. Published experimental results report similar minor tissue responses to a variety of injected biodegradable microcapsules.

Treatment of Tuberculosis Using a Combination of Sustained-Release Rifampin-Loaded Microspheres and Oral Dosing with Isoniazid

“…The poly(lactide-co-glycolide) microspheres allow greater flexibility with respect to the timed release of encapsulated material and are more stable than liposomes (22). While biological degradation of poly(lactide-co-glycolide) microspheres is well understood (26,27), biological degradation of liposomes is not. In addition, microspheres can be formulated to hold a larger amount of drug for longer sustained release than liposomes, on a weight basis comparison (20,29).…”

“…Microsphere technology has the capability of accomplishing these goals by achieving intracellular delivery of antimycobacterial drugs and allowing programmed controlled release over a prolonged period (24). As discussed in our previous publications, the microsphere formulations used in these studies are known to be biocompatible (26,27,28) and capable of degradation to lactic and glycolic acids by nonenzymatic reactions (24). This technology has been used for sustained delivery of various biological components, including antigens, steroids, peptides, proteins, and antibiotics (1,3,9,10,11,12,14,15,21,23,25).…”

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).…”

Next generation vaccines: single-dose encapsulated vaccines for improved global immunisation coverage and efficacy

“…PLGA is the preferred polymer for vaccine delivery as it is safe, immunologically inert and can easily be manipulated to achieve many desired characteristics [13]. Injection of PLGA microcapsules often results in a local inflammatory foreign‐body response, but these reactions are generally mild and resolve over time [35,36]. PLGA is a negatively charged polymer consisting of repeat monomers of lactic and glycolic acid.…”