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Pharmaceutical Research

, Volume 32, Issue 4, pp 1341–1353 | Cite as

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

  • Nitesh K. Kunda
  • Iman M. Alfagih
  • Sarah Rachel Dennison
  • Hesham M. Tawfeek
  • Satyanarayana Somavarapu
  • Gillian A. Hutcheon
  • Imran Y. SaleemEmail author
Research Paper

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.

KEY WORDS

dry powder inhalation nanoparticles pulmonary delivery spray drying vaccines 

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

Notes

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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Nitesh K. Kunda
    • 1
  • Iman M. Alfagih
    • 1
    • 2
  • Sarah Rachel Dennison
    • 3
  • Hesham M. Tawfeek
    • 4
  • Satyanarayana Somavarapu
    • 5
  • Gillian A. Hutcheon
    • 1
  • Imran Y. Saleem
    • 1
    Email author
  1. 1.Formulation and Drug Delivery ResearchSchool of Pharmacy and Biomolecular Sciences, Liverpool John Moores UniversityLiverpoolUK
  2. 2.Department of PharmaceuticsCollege of Pharmacy, King Saud UniversityRiyadhSaudi Arabia
  3. 3.Research and InnovationUniversity of Central LancashirePrestonUK
  4. 4.Department of Industrial Pharmacy, Faculty of PharmacyAssiut UniversityAssiutEgypt
  5. 5.Department of PharmaceuticsSchool of Pharmacy, University College LondonLondonUK

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