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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

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Acknowledgements

This work was supported by the Basic Science Research Program (2020R1A2B5B03002344), Korea Research Fellowship Program (2020H1D3A1A04105814), and Bio & Medical Technology Development Program (2018M3A9E2024579) through the National Research Foundation of Korea funded by the Ministry of Science and ICT (MSIT), Republic of Korea, and the Korea Medical Device Development Fund grant funded by the Korean government (MSIT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (202012D21-02 and 202011A05-05).

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Conceptualization, WP and DKH; methodology, J-KK., E-JG, K-WK; validation, H-JO and JH; formal analysis, E-JG, K-WK, H-JO.; investigation, J-KK; re-sources, DKH and WP; data curation, J-KK, E-JG., and K-WK.; writing—original draft preparation, J-KK; writing—review and editing, JH, DKH, and WP; visualization, E-JG; supervision, DKH and WP; project administration, DKH and WP; funding acquisition, DKH and WP All authors have read and agreed to the published version of the manuscript.

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Correspondence to Dong Keun Han or Wooram Park.

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Kim, JK., Go, EJ., Ko, KW. et al. PLGA Microspheres Containing Hydrophobically Modified Magnesium Hydroxide Particles for Acid Neutralization-Mediated Anti-Inflammation. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00338-z

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Keywords

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