Biodegradable Magnesium-Incorporated Poly(L-lactic acid) Microspheres for Manipulation of Drug Release and Alleviation of Inflammatory Response

Poly(L-lactic acid) (PLLA) and magnesium (Mg) are widely concerned biodegradable materials, but during in vivo implantation, the former produces acidic degradation byproducts and can easily induce inflammation in surrounding tissues, whereas the latter is fast corroded and generates alkaline products. The purpose of this study is to develop Mg/PLLA composite microspheres as a novel delivery system, in which Mg particles are used to regulate the drug release profile and suppress PLLA-induced inflammatory response. Morphological observation shows that multiple Mg particles are dispersed both on the surface and in the interior of composite microspheres. In vitro release study indicates that by varying the Mg contents or its particle sizes, the internal connectivity of composite microspheres is changed during hydrolytic degradation, and drug delivery can be facilely manipulated with tunable release patterns. In vivo release study further confirms the feasibility of Mg/PLLA microspheres for tailoring drug release in a physiological environment. The animal experiment reveals that Mg particles can alleviate macrophage infiltration and inflammatory cytokine expression. These results demonstrate the availability of using biodegradable Mg particles to manipulate drug release as well as alleviate PLLA-induced inflammation. The present Mg/PLLA composite microspheres have potential applications in controlled delivery of various therapeutic agents, especially some growth factors, for bone regeneration.