Development of a Spray-Dried Formulation of Peptide-Dna Nanoparticles into a Dry Powder for Pulmonary Delivery Using Factorial Design

Miftakul Munir, Vicky L. Kett, Nicholas J. Dunne, Helen O. McCarthy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Background: Gene therapy via pulmonary delivery holds the potential to treat various lung pathologies. To date, spray drying has been the most promising method to produce inhalable powders. The present study determined the parameters required to spray dry nanoparticles (NPs) that contain the delivery peptide, termed RALA (N-WEARLARALARALARHLARALARALRACEA-C), complexed with plasmid DNA into a dry powder form designed for inhalation. 

Methods: The spray drying process was optimised using full factorial design with 19 randomly ordered experiments based on the combination of four parameters and three centre points per block. Specifically, mannitol concentration, inlet temperature, spray rate, and spray frequency were varied to observe their effects on process yield, moisture content, a median of particle size distribution, Z-average, zeta potential, encapsulation efficiency of DNA NPs, and DNA recovery. The impact of mannitol concentration was also examined on the spray-dried NPs and evaluated via biological functionality in vitro. 

Results: The results demonstrated that mannitol concentration was the strongest variable impacting all responses apart from encapsulation efficiency. All measured responses demonstrated a strong dependency on the experimental variables. Furthermore, spray drying with the optimal variables in combination with a low mannitol concentration (1% and 3%, w/v) produced functional RALA/pDNA NPs. 

Conclusion: The optimal parameters have been determined to spray dry RALA/pDNA NPs into an dry powder with excellent biological functionality, which have the potential to be used for gene therapy applications via pulmonary delivery.

Original languageEnglish
JournalPharmaceutical Research
Early online date19 Apr 2022
Publication statusEarly online date - 19 Apr 2022

Bibliographical note

Funding Information:
This study was supported by the Indonesian Endowment Fund for Education (Lembaga Pengelola Dana Pendidikan/LPDP) scholarship.

Publisher Copyright:
© 2022, The Author(s).


  • cell-penetrating peptide
  • dry powder formulation
  • gene delivery
  • pulmonary delivery
  • spray drying

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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