title: Dry powder pulmonary delivery of cationic PGA-co-PDL nanoparticles with surface adsorbed model protein.
abstract: Pulmonary delivery of macromolecules has been the focus of attention as an alternate route of delivery with benefits such as; large surface area, thin alveolar epithelium, rapid absorption and extensive vasculature. In this study, a model protein, bovine serum albumin (BSA) was adsorbed onto cationic PGA-co-PDL polymeric nanoparticles (NPs) prepared by a single emulsion solvent evaporation method using a cationic surfactant didodecyldimethylammonium bromide (DMAB) at 2% w/w (particle size: 128.64±06.01 nm and zeta-potential: +42.32±02.70 mV). The optimum cationic NPs were then surface adsorbed with BSA, NP:BSA (100:4) ratio yielded 10.01±1.19 μg of BSA per mg of NPs. The BSA adsorbed NPs (5 mg/ml) were then spray-dried in an aqueous suspension of L-leucine (7.5 mg/ml, corresponding to a ratio of 1:1.5/NP:L-leu) using a Büchi-290 mini-spray dryer to produce nanocomposite microparticles (NCMPs) containing cationic NPs. The aerosol properties showed a fine particle fraction (FPF, dae<4.46 μm) of 70.67±4.07% and mass median aerodynamic diameter (MMAD) of 2.80±0.21 μm suggesting a deposition in the respiratory bronchiolar region of the lungs.The cell viability was 75.76±03.55% (A549 cell line) at 156.25 μg/ml concentration after 24 h exposure. SDS-PAGE and circular dichroism (CD) confirmed that the primary and secondary structure of the released BSA was maintained. Moreover, the released BSA showed 78.76±1.54% relative esterolytic activity compared to standard BSA.
authors.affiliation: Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom.
authors.forename: Nitesh K
authors.initials: NK
authors.lastname: Kunda
authors.affiliation: Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom; Department of Pharmaceutics, College of Pharmacy, King Saud University, Saudi Arabia.
authors.forename: Iman M
authors.initials: IM
authors.lastname: Alfagih
authors.affiliation: Research and Innovation, University of Central Lancashire, Preston, United Kingdom.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Dennison
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University College London, London, United Kingdom.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Somavarapu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University College London, London, United Kingdom.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Merchant
authors.affiliation: Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Hutcheon
authors.affiliation: Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom. Electronic address: I.Saleem@ljmu.ac.uk.
authors.forename: Imran Y
authors.initials: IY
authors.lastname: Saleem
mesh_terms: D000280:Administration, Inhalation; D000327:Adsorption; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D065546:Drug Liberation; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry*; D011208:Powders; D055550:Protein Stability; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry*; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D011091:Polyesters; D011208:Powders; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C568823:poly(glycerol adipate-co-omega-pentadecalactone); C046112:didodecyldimethylammonium; D012710:Serum Albumin, Bovine
keywords: Dry powder inhalation; Nanoparticles; Proteins; Pulmonary delivery; Spray drying