title: Rifampicin-loaded 'flower-like' polymeric micelles for enhanced oral bioavailability in an extemporaneous liquid fixed-dose combination with isoniazid.
abstract: BACKGROUND
  Coadministration of rifampicin (RIF)/isoniazid (INH) is clinically recommended to improve the treatment of tuberculosis. Under gastric conditions, RIF undergoes fast hydrolysis (a pathway hastened by INH) and oral bioavailability loss.
  
  
  OBJECTIVE
  We aimed to assess the chemical stabilization and the oral pharmacokinetics of RIF nanoencapsulated within poly(ε-caprolactone)-b-PEG-b-poly(ε-caprolactone) 'flower-like' polymeric micelles.
  
  
  METHODS
  The chemical stability of RIF was evaluated in vitro under acid conditions with and without INH, and the oral pharmacokinetics of RIF-loaded micelles in rats was compared with those of a suspension coded by the US Pharmacopeia.
  
  
  RESULTS
  Nanoencapsulation decreased the degradation rate of RIF with respect to the free drug. Moreover, in vivo data showed a statistically significant increase of RIF oral bioavailability (up to 3.3-times) with respect to the free drug in the presence of INH.
  
  
  CONCLUSIONS
  Overall results highlight the potential of this nanotechnology platform to develop an extemporaneous liquid RIF/INH fixed-dose combination suitable for pediatric administration.
authors.affiliation: The Group of Biomaterials & Nanotechnology for Improved Medicines, Department of Pharmaceutical Technology, Faculty of Pharmacy & Biochemistry, University of Buenos Aires, Buenos Aires, Argentina. alesosnik@gmail.com.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Moretton
authors.forename: Christian
authors.initials: C
authors.lastname: Hocht
authors.forename: Carlos
authors.initials: C
authors.lastname: Taira
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosnik
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D005026:Ethylene Glycols / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D007538:Isoniazid / Q000008:administration & dosage*; D008297:Male; D008823:Micelles; D050997:Nanomedicine; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage*; D012995:Solubility; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D004337:Drug Carriers; D005026:Ethylene Glycols; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); C062968:lactide-caprolactone copolymer; D006851:Hydrochloric Acid; D007538:Isoniazid; D012293:Rifampin
keywords: extemporaneous liquid rifampicin/isoniazid fixed-dose combination; improved oral pharmacokinetics; pediatric tuberculosis; poly(ε-caprolactone)-b-PEG-b-poly(ε-caprolactone) ‘flower-like’ polymeric micelle; rifampicin chemical stabilization