Preparation of PLGA Nanoparticles Co-Incorporated with Protein and Hydrophobic Drugs as a Formulation of Oral Immunotherapy

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Abstract
Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) fabricated using a water-in-oil-in-water (w/o/w) double emulsion method can simultaneously encapsulate both hydrophilic proteins and hydrophobic drugs. This dual-loading ability of PLGA NPs is expected to be useful in allergen immunotherapy (AIT). We used the formulation to co-encapsulate a hydrophilic model antigen, ovalbumin (OVA), with hydrophobic drugs including rapamycin (Rapa), suberoylanilide hydroxamic acid (Saha) and bexarotene (Bexa). We successfully prepared NPs of approximately 100[ ]nm in diameter and co-encapsulated OVA and the hydrophobic drugs. The NPs remained in the intestinal tract for up to 4[ ]h following oral administration. We found that the NPs showed minimal release of the contents in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and maintained stability without aggregation or degradation for 8[ ]h. These findings suggest that the NPs have the potential to serve as oral carriers for various hydrophobic drugs and antigens, while maintaining stability in gastrointestinal (GI) environments.
Funding Information
  • Japan Society for the Promotion of Science (20H05876, 20H05872)
  • Japan Society for the Promotion of Science (22J12057)

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