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Exosome-loaded degradable polymeric microcapsules for the treatment of vitreoretinal diseases

Han Bao1,2, Ying Tian1,2, Haixin Wang1

  • 1State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China.

Nature Biomedical Engineering
|October 23, 2023
PubMed

Insights

Degradable microcapsules loaded with exosomes show therapeutic potential for vitreoretinal diseases. These exosome-encapsulating microcapsules restore retinal thickness and reduce inflammation, offering new treatment options.

Area of Science:

  • Biomedical Engineering
  • Ophthalmology
  • Regenerative Medicine

Background:

  • Cell-based therapies for vitreoretinal diseases often rely on paracrine mechanisms.
  • Exosomes mediate paracrine signaling, while microcapsules offer sustained release and degradation.
  • Developing advanced drug delivery systems is crucial for treating complex eye conditions.

Purpose of the Study:

  • To investigate the therapeutic efficacy of exosome-loaded degradable poly(lactic-co-glycolic acid) microcapsules for vitreoretinal diseases.
  • To evaluate the sustained release of exosomes and the degradation profile of the microcapsules.
  • To assess the potential of this novel therapeutic approach in preclinical models.

Main Methods:

  • Fabrication of micrometric pore poly(lactic-co-glycolic acid) microcapsules encapsulating exosomes derived from mesenchymal stem cells or regulatory T cells.
  • Intravitreal injection of microcapsules in mouse models of retinal ischemia-reperfusion injury and mycobacterial uveitis.
  • Assessment of retinal thickness restoration and inflammatory cell reduction in treated subjects.
  • Evaluation of exosome release kinetics and microcapsule degradation over time.

Main Results:

  • Intravitreal injection of exosome-loaded microcapsules in a mouse model of retinal ischemia-reperfusion injury led to sustained exosome release and restored retinal thickness.
  • In mouse and non-human primate models of mycobacterial uveitis, the microcapsules significantly reduced inflammatory cell levels.
  • The microcapsules demonstrated controlled degradation and exosome release for over one month.
  • Lyophilized exosome-encapsulating microcapsules were successfully prepared, indicating potential for storage and transport.

Conclusions:

  • Exosome-loaded degradable microcapsules represent a promising therapeutic strategy for vitreoretinal diseases.
  • This delivery system effectively restores retinal structure and modulates inflammation in preclinical models.
  • The lyophilization capability suggests practical advantages for clinical application in ophthalmology.

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