title: Respirable rifampicin-based microspheres containing isoniazid for tuberculosis treatment.
abstract: The purpose of this investigation was to develop small microspheres for delivering antimycobacterial drugs to infected host macrophages. Rifampicin-based microparticles were prepared. The drug was covalently linked to acrylic moieties to obtain a polymerizable derivative for the preparation of materials useful as drug delivery systems that then were loaded with isoniazid acting in synergy with rifampicin. Their antitubercular activity was determined in vitro. Fourier transform infrared spectroscopy confirmed hydrogel structure. Morphological analysis showed microparticles with spherical shape and homogeneous surface. In vitro release studies were performed in media simulating physiologic pH (7.4) and endosomal of alveolar macrophages pH (5.2). A similar amount of isoniazid was delivered within the first 6 h at both pHs, while a smaller amount of the drug was delivered at pH 7.4 in the last phase of the study. In vitro antitubercular activity showed a behavior comparable to that of rifampicin and isoniazid free. Bioactive swelling matrices, showing a high swelling degree into a medium miming intra alveolar environment, were obtained. They could be applied for their antitubercular activity.
authors.affiliation: Department of Pharmaceutical Sciences, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cassano
authors.forename: Sonia
authors.initials: S
authors.lastname: Trombino
authors.forename: Teresa
authors.initials: T
authors.lastname: Ferrarelli
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Mauro
authors.forename: Cristina
authors.initials: C
authors.lastname: Giraldi
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
authors.forename: Nevio
authors.initials: N
authors.lastname: Picci
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012293:Rifampin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013055:Spectrophotometry, Infrared; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007538:Isoniazid; D012293:Rifampin