title: Impact of drug administration route on drug delivery and distribution into the lung: an imaging mass spectrometry approach.
abstract: During the last decade, significant technological improvements in mass spectrometry have had a great impact on drug discovery. The development of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) has set a new frontier for the study of the distribution of endogenous and exogenous molecules present within a tissue. MALDI-IMS is a surface sampling technique that allows not only the detection of multiple analytes but also gives the spatial distribution of those analytes. Active compounds for pulmonary disease need an optimal and well-studied delivery into the lungs, in order to assure distribution with greater penetration into the peripheral or the alveolar region of the lung to maximize the therapeutic effects. IMS is very useful in the field of drug discovery, showing drug delivery and distribution in the body and organs. In this study, we present a comparison between two different ways of carrying out pulmonary drug administration: inhalation of a nebulized aerosol of aqueous drug solutions and intratracheal administration, which is much simpler, not expensive and commonly used during in vivo screening. Tiotropium bromide is a long-acting anticholinergic medicine used for maintenance treatment of chronic obstructive pulmonary disease. In the present work, tiotropium was administered by nebulization and by intratracheal instillation to guinea pigs at doses able to induce significant anti-bronchoconstrictive activity. Lung samples were dissected, frozen, cryosectioned and coated with matrix (α-hydroxy-cinnamic acid). IMS analyses were performed using a MALDI-LTQ-Orbitrap XL. Using this technique we were able to compare different distributions of the drug depending on the method of administration.
authors.affiliation: Centro di servizi di spettrometria di massa (CISM), University of Florence, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zecchi
authors.affiliation: Chiesi Farmaceutici SpA, Corporate Preclinical R&D-FABER Project Group, Florence, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Trevisani
authors.affiliation: Chiesi Farmaceutici SpA, Corporate Preclinical R&D-FABER Project Group, Florence, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pittelli
authors.affiliation: Chiesi Farmaceutici SpA, Corporate Preclinical R&D-FABER Project Group, Florence, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Pedretti
authors.affiliation: Chiesi Farmaceutici SpA, Corporate Preclinical R&D-FABER Project Group, Florence, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Manni
authors.affiliation: Centro di servizi di spettrometria di massa (CISM), University of Florence, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pieraccini
authors.affiliation: Chiesi Farmaceutici SpA, Corporate Preclinical R&D-Analytics and Early Formulations Department, Parma, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pioselli
authors.affiliation: Chiesi Farmaceutici SpA, Corporate Preclinical R&D-Analytics and Early Formulations Department, Parma, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Amadei
authors.affiliation: Centro di servizi di spettrometria di massa (CISM), University of Florence, Italy.
authors.forename: Gloriano
authors.initials: G
authors.lastname: Moneti
authors.affiliation: Chiesi Farmaceutici SpA, Corporate Preclinical R&D-Analytics and Early Formulations Department, Parma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Catinella
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D018680:Cholinergic Antagonists / Q000493:pharmacokinetics; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000379:methods*; D055808:Drug Discovery; D006168:Guinea Pigs; D008168:Lung / Q000378:metabolism*; D008297:Male; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000493:pharmacokinetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D000069447:Tiotropium Bromide; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide