title: Formulation and in vitro characterization of inhalable polyvinyl alcohol-free rifampicin-loaded PLGA microspheres prepared with sucrose palmitate as stabilizer: efficiency for ex vivo alveolar macrophage targeting.
abstract: In this work a new formulation of inhalable rifampicin-loaded PLGA microspheres (RIF-MS) is proposed for the management of tuberculosis treatment. For their formulation, the non-biodegradable polyvinyl alcohol surfactant was replaced with a biodegradable and biocompatible sucrose ester, sucrose palmitate. The effects of critical process and formulation parameters have been investigated and the obtained microspheres were characterized in terms of size, morphology, encapsulation efficiencies and RIF release profile. The optimized RIF-MS showed high drug loading (34.2%, w/w), an aerodynamic diameter compliant with deep lung delivery and an in vitro gradual and almost complete drug release over a week. The drug release data fitted well to the Higuchi models suggesting a drug release governed by Fickian diffusion. The RIF-MS uptake qualitative and quantitative studies on ex vivo rat alveolar macrophages (AM) revealed an efficient internalization of RIF-MS and their location in the perinuclear area. RIF intracellular levels were 7-fold higher in AM incubated with RIF-MS than with an equivalent amount of free RIF.
authors: INSERM, U1070, 1 rue Georges Bonnet, 86022 Poitiers, France.
authors: R
authors: R
authors: Diab
authors: J
authors: J
authors: Brillault
authors: A
authors: A
authors: Bardy
authors: A V L
authors: AV
authors: Gontijo
authors: J C
authors: JC
authors: Olivier
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry*; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D008863:Microspheres; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000008:administration & dosage / Q000737:chemistry*; D013395:Sucrose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000904:Antibiotics, Antitubercular; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C041567:sucrose monopalmitate; D013395:Sucrose; D011142:Polyvinyl Alcohol; D012293:Rifampin