title: Inhalable, large porous PLGA microparticles loaded with paclitaxel: preparation, in vitro and in vivo characterization.
abstract: Large porous particles (LPPs) could be used as a useful carrier for non-invasive delivery to the deep lung. Pulmonary delivery of paclitaxel-loaded LPPs (PTX-LPPs) can help to eliminate the highly complicated and harmful solvent used in PTX parenteral formulations. PTX-LPPs with mass median aerodynamic diameter (MMAD) of 5.74 ± 0.09 μm, high encapsulation efficiency and good aerosolisation properties were produced using ammonium bicarbonate as porogen. Cytotoxicity of PTX-LPPs on A549 and Calu-6 cell lines was comparable with Free-PTX. Endotracheal administration of PTX-LPPs in rats exhibited PTX plasma concentration in the therapeutic range which lasted 4-fold longer than i.v. injection. The bioavailability was measured as 51 ± 7.1%. The lung targeting efficiency (Te) of PTX-LPPs was 11.9-fold higher than i.v. administration. PTX-LPPs could deliver a higher PTX to lung with a non-toxic plasma level in a longer duration which shows their pulmonary delivery suitability.
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shiraz University of Medical Sciences , Shiraz , Iran .
authors.forename: Shohreh
authors.initials: S
authors.lastname: Alipour
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shiraz University of Medical Sciences , Shiraz , Iran .
authors.forename: Hashem
authors.initials: H
authors.lastname: Montaseri
authors.affiliation: b Nanotechnology Research Center and.|c School of Pharmacy, Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Tafaghodi
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D045744:Cell Line, Tumor; D002470:Cell Survival; D004339:Drug Compounding; D006801:Humans; D019344:Lactic Acid; D008168:Lung / Q000378:metabolism; D008297:Male; D008863:Microspheres; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000336:Aerosols; D000972:Antineoplastic Agents, Phytogenic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel
keywords: Inhalable; large porous particle; paclitaxel