Tissue Eng Regen Med.  2021 Aug;18(4):613-522. 10.1007/s13770-021-00338-z.

PLGA Microspheres Containing Hydrophobically Modified Magnesium Hydroxide Particles for Acid NeutralizationMediated Anti-Inflammation

  • 1Department of Biomedical-Chemical Engineering and Biotechnology, The Catholic University of Korea, 43 Jibongro, Wonmi-gu, Bucheon, Gyeonggi 14662, Republic of Korea
  • 2Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi 13488, Republic of Korea
  • 3Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi 14662, Republic of Korea


Poly(lactic-co-glycolic acid) (PLGA) microspheres have been actively used in various pharmaceutical formulations because they can sustain active pharmaceutical ingredient release and are easy to administer into the body using a syringe. However, the acidic byproducts produced by the decomposition of PLGA cause inflammatory reactions in surrounding tissues, limiting biocompatibility. Magnesium hydroxide (MH), an alkaline ceramic, has attracted attention as a potential additive because it has an acid-neutralizing effect.
To improve the encapsulation efficiency of hydrophilic MH, the MH particles were capped with hydrophobic ricinoleic acid (RA-MH). PLGA microspheres encapsulated with RA-MH particles were manufactured by the O/W method. To assess the in vitro cytotoxicity of the degradation products of PLGA, MH/PLGA, and RA-MH/PLGA microspheres, CCK-8 and Live/Dead assays were performed with NIH-3T3 cells treated with different concentrations of their degradation products. in vitro anti-inflammatory effect of RA-MH/PLGA microspheres was evaluated with quantitative measurement of pro-inflammatory cytokines.
The synthesized RA-MH was encapsulated in PLGA microspheres and displayed more than four times higher loading content than pristine MH. The PLGA microspheres encapsulated with RA-MH had an acid-neutralizing effect better than that of the control group. In an in vitro cell experiment, the degradation products obtained from RA-MH/PLGA microspheres exhibited higher biocompatibility than the degradation products obtained from PLGA microspheres. Additionally, the RA-MH/PLGA microsphere group showed an excellent anti-inflammatory effect.
Our results proved that RA-MH-encapsulated PLGA microspheres showed excellent biocompatibility with an anti-inflammatory effect. This technology can be applied to drug delivery and tissue engineering to treat various incurable diseases in the future.


Biodegradable polymers; Poly(lactic-co-glycolic acid); Polymeric microspheres; Magnesium hydroxide; Acid neutralization; Anti-inflammation
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