title: Nasal powders of thalidomide for local treatment of nose bleeding in persons affected by hereditary hemorrhagic telangiectasia.
abstract: In this work nasal powder formulations of thalidomide were designed and studied to be used by persons affected by hereditary hemorrhagic telangiectasia as a complementary anti-epistaxis therapy, with the goal of sustaining the effect obtained with thalidomide oral treatment after its discontinuation for adverse effects. Three nasal powders were prepared using as carriers β-CD or its more hydrophilic derivatives such as hydropropyl-β-CD and sulphobutylether-β-CD and tested with respect to technological and biopharmaceutical features after emission with active and passive nasal powder devices. For all formulated powders, improved dissolution rate was found compared to that of the raw material, making thalidomide promptly available in the nasal environment at a concentration favouring an accumulation in the mucosa. The very limited transmucosal transport measured in vitro suggests a low likelihood of significant systemic absorption. The topical action on bleeding could benefit from the poor absorption and from the fact that about 2-3% of the thalidomide applied on the nasal mucosa was accumulated within the tissue, particularly with the β-CD nasal powder.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Colombo
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bortolotti
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Chiapponi
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Buttini
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Sonvico
authors.affiliation: Department of Internal Medicine, University of Pavia, IRCCS Fondazione Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Invernizzi
authors.affiliation: Department of Internal Medicine, University of Pavia, IRCCS Fondazione Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Quaglia
authors.affiliation: Department of Molecular Medicine, General Biology and Medical Genetics Unit, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Danesino
authors.affiliation: Department of Otorhinolaryngology, IRCCS Fondazione Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pagella
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Russo
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bettini
authors.affiliation: PlumeStars srl, Strada G. Inzani 1, 43125 Parma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Colombo
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy. Electronic address: alessandra.rossi@unipr.it.
authors.forename: A
authors.initials: A
authors.lastname: Rossi
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004844:Epistaxis / Q000188:drug therapy*; D006801:Humans; D009297:Nasal Mucosa / Q000187:drug effects; D011208:Powders / Q000008:administration & dosage*; D011817:Rabbits; D012995:Solubility; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage*; D047392:beta-Cyclodextrins / Q000008:administration & dosage
chemical_list: D004337:Drug Carriers; D011208:Powders; D047392:beta-Cyclodextrins; D013792:Thalidomide
keywords: Cyclodextrins; Hydroxypropyl-β-cyclodextrin (PubChem CID: 44134771); Lecithin (PubChem CID: 57369748); Mucoadhesion; Nasal devices; Nasal powders; Sulphobutylether-β-cyclodextrin (PubChem CID: 91886200); Telangiectasia; Thalidomide; Thalidomide (PubChem CID: 5426); β-cyclodextrin (PubChem CID: 444041)