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Immune Cells Activating Biotin-Decorated PLGA Protein Carrier
Paul R Hartmeier1, Jessica L Kosanovich2, Ketki Y Velankar1
1Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, Pennsylvania 15282, United States.
Molecular Pharmaceutics
|May 27, 2022
Summary
Biotin-modified PLGA nanoparticles (bNPs) effectively deliver proteins and act as self-adjuvanting carriers for subunit vaccines. These nanoparticles stimulate immune cells and are retained in lymph nodes, showing promise for vaccine development.
Area of Science:
- Biomaterials Science
- Immunology
- Nanotechnology
Background:
- Nanoparticle formulations are investigated as subunit vaccine carriers for protein entrapment and adjuvant co-delivery.
- Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are widely studied for controlled release and drug delivery applications.
- PLGA particles have been proposed as effective subunit vaccine carriers.
Purpose of the Study:
- To investigate biotin-modified PLGA nanoparticles (bNPs) as carriers for protein delivery via adsorption.
- To assess the ability of bNPs to stimulate professional antigen-presenting cells (APCs) and their self-adjuvanting properties.
- To evaluate the in vivo biodistribution and cellular uptake of bNPs.
Main Methods:
- Proteins were adsorbed onto bNPs utilizing the biotin-avidin interaction.
- Enzyme activity of captured proteins (horseradish peroxidase) was analyzed.
- In vitro cytokine production (IL-1β, IL-18, IL-12) in APCs stimulated by bNPs was measured.
- Subcutaneous and intranasal administration of bNPs in mice was performed to assess biodistribution and cellular uptake.
Main Results:
- bNPs effectively retained biotinylated proteins (catalase, horseradish peroxidase) via biotin-avidin interaction, preserving enzyme activity.
- bNPs demonstrated self-adjuvanting properties, inducing IL-1β, IL-18, and IL-12 production in APCs, promoting Th1 responses.
- Exposed biotin on bNPs contributed to the observed pro-inflammatory cytokine response.
- Subcutaneously injected bNPs localized to draining lymph nodes for at least 28 days.
- Intranasally delivered bNPs were internalized by dendritic cells and macrophages in a dose-dependent manner.
Conclusions:
- bNPs are capable of adsorbing and retaining proteins while preserving their activity.
- bNPs possess inherent self-adjuvanting properties, stimulating APCs and promoting Th1-type immune responses.
- bNPs exhibit favorable biodistribution and cellular uptake characteristics in vivo.
- These findings support further exploration of bNPs as adjuvanting carriers for subunit vaccine development.
