title: Development of controlled-release cisplatin dry powders for inhalation against lung cancers.
abstract: The present study focuses on the development of dry powders for inhalation as adjuvant chemotherapy in lung cancer treatment. Cisplatin was chosen as a potential candidate for a local treatment as it remains the main platinum component used in conventional chemotherapies, despite its high and cumulative systemic toxicities. Bulk cisplatin was reduced to submicron sizes using high-pressure homogenization, mixed with a solubilized lipid and/or PEGylated component and then spray-dried to produce controlled-release dry powder formulations. The obtained formulations were characterized for their physicochemical properties (particle size and morphology), aerodynamic performance and release profiles. Cisplatin content and integrity were assessed by electrothermal atomic absorption spectrometry and195Pt nuclear magnetic resonance spectroscopy. DPI formulations with cisplatin contents ranging from 48.5 to 101.0% w/w exhibited high fine particle fractions ranging from 37.3% to 51.5% of the nominal dose. Formulations containing cisplatin microcrystals dispersed in solid lipid microparticles based on acceptable triglycerides for inhalation and PEGylated excipients showed a controlled-release for more than 24h and a limited burst effect. These new formulations could provide an interesting approach to increasing and prolonging drug exposure in the lung while minimizing systemic toxicities.
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, CP207, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Campus Plaine, B-1050 Brussels, Belgium. Electronic address: vincent.levet@ulb.ac.be.
authors.forename: Vincent
authors.initials: V
authors.lastname: Levet
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, CP207, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Campus Plaine, B-1050 Brussels, Belgium.
authors.forename: Rémi
authors.initials: R
authors.lastname: Rosière
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, CP207, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Campus Plaine, B-1050 Brussels, Belgium.
authors.forename: Romain
authors.initials: R
authors.lastname: Merlos
authors.affiliation: Unité de Chimie des Nanomatériaux (CNANO), Université de Namur, 61 rue de Bruxelles, B-5000 Namur, Belgium.
authors.forename: Luca
authors.initials: L
authors.lastname: Fusaro
authors.affiliation: Laboratoire de Chimie Pharmaceutique Organique, CP205/5, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Campus Plaine, B-1050 Brussels, Belgium.
authors.forename: Gilles
authors.initials: G
authors.lastname: Berger
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, CP207, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Campus Plaine, B-1050 Brussels, Belgium.
authors.forename: Karim
authors.initials: K
authors.lastname: Amighi
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, CP207, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Campus Plaine, B-1050 Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wauthoz
mesh_terms: D000280:Administration, Inhalation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D003890:Desiccation / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D058995:Dry Powder Inhalers / Q000379:methods; D005079:Excipients / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011208:Powders / Q000008:administration & dosage* / Q000737:chemistry*; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D011208:Powders; D011092:Polyethylene Glycols; D002945:Cisplatin
keywords: Cisplatin; Cisplatin (PubChem CID:441203); Controlled-release; Dry powder inhaler; Lung cancer chemotherapy; Pulmonary delivery; Solid lipid microparticles; distearoyl phosphoethanolamine polyethylene glycol 2000, sodium salt (DSPE-mPEG-2000, PubChem CID:86278270); tristearin (PubChem CID:11146), alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS, PubChem CID:71406)