title: Nanopolymersomes as potential carriers for rifampicin pulmonary delivery.
abstract: Tuberculosis (TB) has been stated as "the greatest killer worldwide due to a single infectious agent" behind the human immunodeficiency virus. Standard short-term treatment includes the oral administration of a combination of "first-line" drugs. However, poor-patient compliance and adherence to the long-term treatments represent one of the mayor drawbacks of the TB therapy. An alternative to the oral route is the pulmonary delivery of anti-TB drugs for local or systemic administration. Nanotechnology offers an attractive platform to develop novel inhalable/respirable nanocarriers. The present investigation was focused on the encapsulation of rifampicin (RIF) (a "first-line" anti-TB drug) within nanopolymersomes (nanoPS) employing di- and tri-block poly(ethylene glycol) (PEG)-poly(ɛ-caprolactone) (PCL) based copolymers as biomaterials. The derivatives presented a number-average molecular weight between 12.2 KDa and 30.1 KDa and a hydrophobic/hydrophilic balance between 0.56 and 0.99. The nanoPS were able to enhance the apparent RIF aqueous solubility (up to 4.62 mg/mL) where the hydrodynamic diameters of the drug-loaded systems (1% w/v) were ranged between 65.8 nm and 94 nm at day 0 as determined by dynamic light scattering (DLS). Then, RIF-loaded systems demonstrated as excellent colloidal stability in aqueous media over 14 days with a spherical morphology as determined by transmission electron microscopy (TEM). Furthermore, RIF-loaded nano-sized PS promoted drug accumulation in macrophages (RAW 264.7) versus a drug solution representing promising results for a potential TB inhaled therapy.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina; Science Research Council (CONICET), Buenos Aires, Argentina. Electronic address: marcelamoretton@gmail.com.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Moretton
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina; Science Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Cagel
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina; Science Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Bernabeu
authors.affiliation: Department of Biological Chemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina; Science Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: Lorena
authors.initials: L
authors.lastname: Gonzalez
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina; Science Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Chiappetta
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002460:Cell Line; D004337:Drug Carriers; D008168:Lung; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D012293:Rifampin / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000995:Antitubercular Agents; D004337:Drug Carriers; D012293:Rifampin
keywords: Inhalable antitubercular therapy; Nanopolymersomes; Poly(ethylene glycol)-poly(epsilon-caprolactone) copolymer; Rifampicin; Tuberculosis