title: Biopharmaceutical in vitro characterization of CPZEN-45, a drug candidate for inhalation therapy of tuberculosis.
abstract: BACKGROUND
  The caprazamycin derivative, CPZEN-45 has previously demonstrated antitubercular activity against Mycobacterium tuberculosis H37Rv. Here, the authors report a basic biopharmaceutical characterization of the compound focusing on in vitro permeability and cytotoxicity, with respect to the suitability of CPZEN-45 hydrochloride for inhalation treatment of tuberculosis.
  
  
  RESULTS
  MTT assays confirmed that CPZEN-45 HCl had no acute cytotoxic effects up to 3 mg/ml. In transport studies, apparent permeability coefficients of CPZEN-45 HCl across Calu-3 monolayers in absorptive and secretive directions were 0.43 ± 0.20 × 10(-6) cm/s and 0.38 ± 0.12 × 10(-6) cm/s, respectively. Across ATI-like monolayers, apparent permeability values were 12.10 ± 4.31 × 10(-6) cm/s and 8.50 ± 1.83 × 10(-6) cm/s. CPZEN-45 HCl formed colloidal complexes at concentrations above 0.38 mg/ml; however, these complexes were not micelles, as assessed by Orange OT encapsulation assay.
  
  
  CONCLUSIONS
  CPZEN-45 is an interesting new drug candidate with potential to be used in aerosol therapy of tuberculosis.
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences, Trinity College Dublin, Ireland.
authors.forename: Johanna J
authors.initials: JJ
authors.lastname: Salomon
authors.forename: Pauline
authors.initials: P
authors.lastname: Galeron
authors.forename: Nanette
authors.initials: N
authors.lastname: Schulte
authors.forename: Paul R
authors.initials: PR
authors.lastname: Morow
authors.forename: Diana
authors.initials: D
authors.lastname: Severynse-Stevens
authors.forename: Hanno
authors.initials: H
authors.lastname: Huwer
authors.forename: Nicole
authors.initials: N
authors.lastname: Daum
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hickey
authors.forename: Carsten
authors.initials: C
authors.lastname: Ehrhardt
mesh_terms: D000280:Administration, Inhalation; D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001381:Azepines / Q000493:pharmacokinetics / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008823:Micelles; D010539:Permeability; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D001381:Azepines; C583520:CPZEN-45; D008823:Micelles