title: Drug permeation and cellular interaction of amino acid-coated drug combination powders for pulmonary delivery.
abstract: The effect of three amino acid coatings (L-leucine, L-valine and L-phenylalanine) on particle integrity, aerosolization properties, cellular interaction, cytocompatibility, and drug permeation properties of drug combination powder particles (beclomethasone dipropionate and salbutamol sulphate) for dry powder inhalation (DPI) was investigated. Particles with crystalline L-leucine coating resulted in intact separated particles, with crystalline L-valine coating in slightly sintered particles and with amorphous L-phenylalanine coating in strongly fused particles. The permeation of beclomethasone dipropionate across a Calu-3 differentiated cell monolayer was increased when compared with its physical mixture. Drug crystal formation was also observed on the Calu-3 cell monolayer. The L-leucine coated particles were further investigated for cytocompatibility in three human pulmonary (Calu-3, A549 and BEAS-2B) and one human macrophage (THP-1) cell lines, where they showed excellent tolerability. The l-leucine coated particles were also examined for their ability to elicit reactive oxygen species in pulmonary BEAS-2B and macrophage THP-1 cell lines. The study showed the influence of the amino acid coatings for particle formation and performance and their feasibility for combination therapy for pulmonary delivery.
authors.affiliation: Aalto University, School of Science, P.O. Box 15100 (Puumiehenkuja 2A), FI-00076, Aalto, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Vartiainen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Finland. Electronic address: luis.bimbo@helsinki.fi.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Bimbo
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Finland.
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: Aalto University, School of Science, P.O. Box 15100 (Puumiehenkuja 2A), FI-00076, Aalto, Finland.
authors.forename: Esko I
authors.initials: EI
authors.lastname: Kauppinen
authors.affiliation: Aalto University, School of Science, P.O. Box 15100 (Puumiehenkuja 2A), FI-00076, Aalto, Finland. Electronic address: janne.raula@aalto.fi.
authors.forename: Janne
authors.initials: J
authors.lastname: Raula
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry; D001507:Beclomethasone / Q000008:administration & dosage* / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D004338:Drug Combinations; D058995:Dry Powder Inhalers; D006801:Humans; D007930:Leucine / Q000008:administration & dosage* / Q000737:chemistry; D010649:Phenylalanine / Q000008:administration & dosage* / Q000737:chemistry; D011208:Powders; D017382:Reactive Oxygen Species / Q000378:metabolism; D014633:Valine / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004338:Drug Combinations; D011208:Powders; D017382:Reactive Oxygen Species; D010649:Phenylalanine; D007930:Leucine; D014633:Valine; D001507:Beclomethasone; D000420:Albuterol
keywords: Amino acid; Cell viability; Drug delivery; Epithelial cell; Inhalation