title: Pulmonary delivery of antitubercular drugs using spray-dried lipid-polymer hybrid nanoparticles.
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.
authors.affiliation: a Department of Research Innovation & Consultancy , Punjab Technical University , Kapurthala , India.|b IIPC Lab, Department of Pharmaceutics , ISF College of Pharmacy , Moga, Punjab , India.
authors.forename: Ankur
authors.initials: A
authors.lastname: Bhardwaj
authors.affiliation: b IIPC Lab, Department of Pharmaceutics , ISF College of Pharmacy , Moga, Punjab , India.
authors.forename: Shuchi
authors.initials: S
authors.lastname: Mehta
authors.affiliation: d Division of Microbiology, CSIR-CDRI , Lucknow, Uttar Pradesh , India.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Yadav
authors.affiliation: d Division of Microbiology, CSIR-CDRI , Lucknow, Uttar Pradesh , India.
authors.forename: Sudheer K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: c Preclinical Drug Development Platform, North West University , Potchefstroom , South Africa.
authors.forename: Anne
authors.initials: A
authors.lastname: Grobler
authors.affiliation: b IIPC Lab, Department of Pharmaceutics , ISF College of Pharmacy , Moga, Punjab , India.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Goyal
authors.affiliation: b IIPC Lab, Department of Pharmaceutics , ISF College of Pharmacy , Moga, Punjab , India.|c Preclinical Drug Development Platform, North West University , Potchefstroom , South Africa.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Mehta
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002939:Ciprofloxacin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007538:Isoniazid / Q000737:chemistry / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000995:Antitubercular Agents; D008055:Lipids; D002939:Ciprofloxacin; D007538:Isoniazid
keywords: dry powder inhaler; lipid; nanoparticles; spray drying; tuberculosis; uptake