Formulation and Characterization of Microcapsules Encapsulating PC12 Cells as a Prospective Treatment Approach for Parkinson's Disease

AAPS PharmSciTech. 2021 May 7;22(4):149. doi: 10.1208/s12249-021-02007-9.

Abstract

Parkinson's disease (PD) is the second most common neurological disorder, associated with decreased dopamine levels in the brain. The goal of this study was to assess the potential of a regenerative medicine-based cell therapy approach to increase dopamine levels. In this study, we used rat adrenal pheochromocytoma (PC12) cells that can produce, store, and secrete dopamine. These cells were microencapsulated in the selectively permeable polymer membrane to protect them from immune responses. For fabrication of the microcapsules, we used a modified Buchi spray dryer B-190 that allows for fast manufacturing of microcapsules and is industrially scalable. Size optimization of the microcapsules was performed by systematically varying key parameters of the spraying device. The short- and long-term stabilities of the microcapsules were assessed. In the in vitro study, the cells were found viable for a period of 30 days. Selective permeability of the microcapsules was confirmed via dopamine release assay and micro BCA protein assay. We found that the microcapsules were permeable to the small molecules including dopamine and were impermeable to the large molecules like BSA. Thus, they can provide the protection to the encapsulated cells from the immune cells. Griess's assay confirmed the non-immunogenicity of the microcapsules. These results demonstrate the effective fabrication of microcapsules encapsulating cells using an industrially scalable device. The microcapsules were stable, and the cells were viable inside the microcapsules and were found to release dopamine. Thus, these microcapsules have the potential to serve as the alternative or complementary treatment approach for PD.

Keywords: PC12 cells; Parkinson’s disease; cell viability; dopamine release assay; microencapsulation.

MeSH terms

  • Aluminum Compounds / administration & dosage
  • Aluminum Compounds / chemical synthesis*
  • Aluminum Compounds / metabolism
  • Animals
  • Brain / metabolism
  • Capsules / administration & dosage
  • Capsules / chemical synthesis*
  • Capsules / metabolism
  • Cell Encapsulation / methods*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cell- and Tissue-Based Therapy / methods*
  • Dopamine / metabolism
  • Mice
  • PC12 Cells
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / therapy
  • Polymers / administration & dosage
  • Polymers / chemical synthesis
  • Polymers / metabolism
  • Prospective Studies
  • RAW 264.7 Cells
  • Rats
  • Sodium Compounds / administration & dosage
  • Sodium Compounds / chemical synthesis*
  • Sodium Compounds / metabolism
  • Treatment Outcome

Substances

  • Aluminum Compounds
  • Capsules
  • Polymers
  • Sodium Compounds
  • sodium aluminum hydride
  • Dopamine