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Bovine Serum Albumin Adsorbed PGA-co-PDL Nanocarriers for Vaccine Delivery via Dry Powder Inhalation

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

APCs:

Antigen presenting cells

BSA:

Bovine serum albumin

DCs:

Dendritic cells

DoE:

Design of experiment

LN:

Lymph node

NPs:

Nanoparticles

NCMPs:

Nanocomposite microparticles

PGA-co-PDL:

Poly(glycerol adipate-co-ω-pentadecalactone)

PLA:

Polylactide or poly-L-lactic acid

PLGA:

Poly lactic-co-glycolic-acid

PVA:

Polyvinyl alcohol

SD:

Spray-drying

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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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Authors and Affiliations

  1. Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James Parson Building, Byrom Street, Liverpool, L3 3AF, UK

    Nitesh K. Kunda, Iman M. Alfagih, Gillian A. Hutcheon & Imran Y. Saleem

  2. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Iman M. Alfagih

  3. Research and Innovation, University of Central Lancashire, Preston, UK

    Sarah Rachel Dennison

  4. Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt

    Hesham M. Tawfeek

  5. Department of Pharmaceutics, School of Pharmacy, University College London, London, UK

    Satyanarayana Somavarapu

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  1. Nitesh K. Kunda
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  2. Iman M. Alfagih
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  4. Hesham M. Tawfeek
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  5. Satyanarayana Somavarapu
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  7. Imran Y. Saleem
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Correspondence to Imran Y. Saleem.

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Kunda, N.K., Alfagih, I.M., Dennison, S.R. et al. Bovine Serum Albumin Adsorbed PGA-co-PDL Nanocarriers for Vaccine Delivery via Dry Powder Inhalation. Pharm Res 32, 1341–1353 (2015). https://doi.org/10.1007/s11095-014-1538-5

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  • DOI: https://doi.org/10.1007/s11095-014-1538-5

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