Bovine Serum Albumin Adsorbed PGA-co-PDL Nanocarriers for Vaccine Delivery via Dry Powder Inhalation
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Dry powder vaccine delivery via the pulmonary route has gained significant attention as an alternate route to parenteral delivery. In this study, we investigated bovine serum albumin (BSA) adsorbed poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL polymeric nanoparticles (NPs) within L-leucine (L-leu) microcarriers for dry powder inhalation.
NPs were prepared by oil-in-water single emulsion-solvent evaporation and particle size optimised using Taguchi’s design of experiment. BSA was adsorbed onto NPs at different ratios at room temperature. The NPs were spray-dried in aqueous suspension of L-leu (1:1.5) using a Büchi-290 mini-spray dryer. The resultant nanocomposite microparticles (NCMPs) were characterised for toxicity (MTT assay), aerosolization (Next Generation Impactor), in vitro release study and BSA was characterized using SDS-PAGE and CD respectively.
NPs of size 128.50 ± 6.57 nm, PDI 0.07 ± 0.03 suitable for targeting lung dendritic cells were produced. BSA adsorption for 1 h resulted in 10.23 ± 1.87 μg of protein per mg of NPs. Spray-drying with L-leu resulted in NCMPs with 42.35 ± 3.17% yield. In vitro release study at 37°C showed an initial burst release of 30.15 ± 2.33% with 95.15 ± 1.08% over 48 h. Aerosolization studies indicated fine particle fraction (FPF%) dae < 4.46 μm as 76.95 ± 5.61% and mass median aerodynamic diameter (MMAD) of 1.21 ± 0.67 μm. The cell viability was 87.01 ± 14.11% (A549 cell line) and 106.04 ± 21.14% (16HBE14o- cell line) with L-leu based NCMPs at 1.25 mg/ml concentration after 24 h treatment. The SDS-PAGE and CD confirmed the primary and secondary structure of the released BSA.
The results suggest that PGA-co-PDL/L-leu NCMPs may be a promising carrier for pulmonary vaccine delivery due to excellent BSA adsorption and aerosolization behaviour.
KEY WORDSdry powder inhalation nanoparticles pulmonary delivery spray drying vaccines
Antigen presenting cells
Bovine serum albumin
Design of experiment
Polylactide or poly-L-lactic acid
ACKNOWLEDGMENTS AND DISCLOSURES
We would like to thank Dr Mark Murphy (Liverpool John Moores University, Liverpool, UK) for his help with confocal microscopy studies
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