Pulmonary delivery of antitubercular drugs using spray-dried lipid–polymer hybrid nanoparticles

Ankur Bhardwaj, Shuchi Mehta, Shailendra Yadav, Sudheer K. Singh, Anne Grobler, Amit Kumar Goyal, Abhinav Mehta

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

The present study aimed to develop lipid–polymer hybrid nanoparticles (LPNs) for the combined pulmonary delivery of isoniazid (INH) and ciprofloxacin hydrochloride (CIP HCl). Drug-loaded LPNs were prepared by the double-emulsification solvent evaporation method using the three-factor three-level Box–Behnken design. The optimized formulation had a size of 111.81 ± 1.2 nm, PDI of 0.189 ± 1.4, and PDE of 63.64 ± 2.12% for INH-loaded LPN, and a size of 172.23 ± 2.31 nm, PDI of 0.169 ± 1.23, and PDE of 68.49 ± 2.54% for CIP HCl-loaded LPN. Drug release was found to be sustained and controlled at lower pH and followed the Peppas model. The in vitro uptake study in alveolar macrophage (AM) showed that uptake of the drugs was increased significantly if administered in the form of LPN. The stability study proved the applications of adding PLGA in LPN as the polymeric core, which leads to a much more stable product as compared to other novel drug delivery systems. Spray drying was done to produce an inhalable, dry, powdered form of drug-loaded LPN. The spray-dried (SD) powder was equally capable of producing nano-aggregates having morphology, density, flowability and reconstitutibility in the range ideal for inhaled drug delivery. The nano aggregates produced by spray drying manifested their aerosolization efficiency in terms of the higher emitted dose and fine particle fraction with lower mass median aerodynamic diameter. The in vivo study using pharmacokinetic and pharmacodynamic approaches revealed that maximum internalization efficiency was achieved by delivering LPN in SD powdered forms by pulmonary route.
Original languageEnglish (US)
Pages (from-to)1544-1555
Number of pages12
JournalArtificial Cells, Nanomedicine and Biotechnology
Volume44
Issue number6
DOIs
StatePublished - Aug 17 2016
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-10-12

ASJC Scopus subject areas

  • Biotechnology
  • Biomedical Engineering
  • Pharmaceutical Science
  • Medicine (miscellaneous)

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