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

Abstract

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.

Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches

“…In another study, Mg particles were mixed in a PDLLA matrix to enhance MSC viability and osteogenic differentiation. The dissolution of Mg ions from composites was proven to be able to regulate the macrophage-induced inflammatory response evoked by PDLLA degradation components [ 145 , 146 ]. However, micron-size magnesium particles could be engulfed by macrophages, resulting in the necrosis of macrophages and the release of inflammatory cytokines [ 147 ].…”

Micro‐/Nano‐Structures on Biodegradable Magnesium@PLGA and Their Cytotoxicity, Photothermal, and Anti‐Tumor Effects

“…After irradiating for 4 min at a laser intensity of 0.7 W cm −2 , the temperature of Mg@PLGA microspheres and nanospheres with Mg concentration of 60 mg mL −1 increases from 25 °C to 40 °C, which is sufficient for photothermal therapy (Figure 3b,e). [ 3,10,15–43 ] After irradiating for 10 min, the temperature of both spheres increases from 25 °C to 55 °C. Both the rising and declining of temperature in response to laser switching on and off are prompt and identical; moreover, the photothermal response of Mg@PLGA microspheres and nanospheres are reliable for multiple repeated cycles with laser on‐and‐off (Figure 3c,f).…”

“…[ 16–19,21 ] Typically, polymer/solvent solutions with magnetism nanoparticles and aqueous solutions are emulsified by ultrasonic homogenization; after solvent evaporation, aqueous suspensions of nanosized Mg@polymer particles are obtained. [ 22 ] However, the top‐down high‐power homogenization with high shear leads to a low encapsulation efficiency of Mg in polymer nanoparticles, and a broad size distribution of resultant Mg@polymer particles. [ 23 ] The less‐exquisite control over the content loading and size distribution makes the cellular uptake inefficient, partially because particles with either too small or too big size can be easily cleared by the immune system, spleen, and kidney.…”

An overview of the development of composites containing Mg and Zn for drug delivery

“…Yang et al [185] assembled flower-mesoporous carbon (FPCS)-magnetic Fe 3 O 4 and pH-sensitive ZnO nanoparticles to construct the FPCS-Fe 3 O 4 -ZnO composite as microwave and pH bi-triggered drug carrier. Yang et al [186] incorporated Mg particles into poly (l-lactic acid) (PLLA) microspheres to suppress inflammatory response induced by PLLA and regulate the drug release profile. It was shown that the internal connectivity of the microspheres was altered during hydrolytic degradation by changing the Mg particle sizes and contents, resulting in manipulating drug delivery with tunable release patterns.…”