title: Rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: Physicochemical and in vitro studies.
abstract: Systemic administration of antitubercular drugs can be complicated by off-target toxicity to cells and tissues that are not infected by Mycobacterium tuberculosis . Delivery of antitubercular drugs via nanoparticles directly to the infected cells has the potential to maximize efficacy and minimize toxicity. The present work demonstrates the potential of solid lipid nanoparticles (SLN) as a delivery platform for rifabutin (RFB). Two different RFB-containing SLN formulations were produced using glyceryl dibehenate or glyceryl tristearate as lipid components. Full characterization was performed in terms of particle size, encapsulation and loading efficiency, morphology by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) studies. Physical stability was evaluated when formulations were stored at 5 ± 3°C and in the freeze-dried form. Formulations were stable throughout lyophilization without significant variations on physicochemical properties and RFB losses. The SLN showed to be able to endure harsh temperature conditions as demonstrated by dynamic light scattering (DLS). Release studies revealed that RFB was almost completely released from SLN. In vitro studies with THP1 cells differentiated in macrophages showing a nanoparticle uptake of 46 ± 3% and 26 ± 9% for glyceryl dibehenate and glyceryl tristearate SLN, respectively. Cell viability studies using relevant lung cell lines (A549 and Calu-3) revealed low cytotoxicity for the SLN, suggesting these could be new potential vehicles for pulmonary delivery of antitubercular drugs.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Nanobiofar Group, Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Spain.
authors.forename: Diana P
authors.initials: DP
authors.lastname: Gaspar
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Vasco
authors.initials: V
authors.lastname: Faria
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Lídia M D
authors.initials: LM
authors.lastname: Gonçalves
authors.affiliation: Colloids and Polymers Physics Group, Condensed Matter Physics Department, Faculty of Physics, University of Santiago de Compostela, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Taboada
authors.affiliation: Nanobiofar Group, Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Remuñán-López
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address: aalmeida@ff.ulisboa.pt.
authors.forename: António J
authors.initials: AJ
authors.lastname: Almeida
mesh_terms: D000280:Administration, Inhalation; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients; D005227:Fatty Acids / Q000737:chemistry*; D005612:Freeze Drying; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D017828:Rifabutin / Q000008:administration & dosage* / Q000494:pharmacology; D012995:Solubility; D013696:Temperature; D014280:Triglycerides / Q000737:chemistry*
chemical_list: D000995:Antitubercular Agents; D004337:Drug Carriers; D005079:Excipients; D005227:Fatty Acids; D014280:Triglycerides; C086409:glyceryl behenate; D017828:Rifabutin; C022618:tristearin
keywords: Cell viability and uptake; Pulmonary administration; Rifabutin; Solid lipid nanoparticles; Stability; Tuberculosis