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. CONCLUSION: CPZEN-45 is an interesting new drug candidate with potential to be used in aerosol therapy of tuberculosis.
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. CONCLUSION:CPZEN-45 is an interesting new drug candidate with potential to be used in aerosol therapy of tuberculosis.
Authors: Ragan A Pitner; Phillip G Durham; Ian E Stewart; Steven G Reed; Gail H Cassell; Anthony J Hickey; Darrick Carter Journal: J Pharm Sci Date: 2019-05-29 Impact factor: 3.534