title: Nanostructured lipid carriers loaded with tributyrin as an alternative to improve anticancer activity of all-trans retinoic acid.
abstract: OBJECTIVE
  All-trans retinoic acid (ATRA) is one of the most successful examples of differentiation agents and histone deacetylase inhibitors, such as tributyrin (TB), are known for their antitumor activity and potentiating action of drugs, such as ATRA. Nanostructured lipid carriers (NLC) represent a promising alternative to the encapsulation of lipophilic drugs such as ATRA. This study aims to develop, characterize and evaluate the cytotoxicity of ATRA-TB-loaded NLC for cancer treatment.
  
  
  METHODS
  The influence of in situ formation of an ion pairing between ATRA and a lipophilic amine (benethamine) on the characteristics of NLC (size, zeta potential, encapsulation efficiency) was evaluated. TB, a butyric acid donor, was used as a component of the lipid matrix. In vitro activity on cell viability and distribution of cell cycle phases were evaluated for MCF-7, MDA-MB-231, HL-60 and Jurkat cell lines.
  
  
  RESULTS
  The presence of the amine significantly increased the encapsulation efficiency of ATRA in NLC. Inhibition of cell viability by TB-ATRA-loaded NLC was more pronounced than the free drug. Analysis of the distribution of cell cycle phases also showed increased activity for TB-ATRA-loaded NLC, with the clear effect of cell cycle arrest in G0/G1 phase transition. The presence of TB played an important role in the activity of the formulation.
  
  
  CONCLUSIONS
  Taken together, these findings suggest that TB-ATRA-loaded NLC represents a promising alternative to intravenous administration of ATRA in cancer treatment.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: Elton Luiz
authors.initials: EL
authors.lastname: Silva
authors.forename: Guilherme
authors.initials: G
authors.lastname: Carneiro
authors.forename: Priscila Albuquerque
authors.initials: PA
authors.lastname: Caetano
authors.forename: Gisele
authors.initials: G
authors.lastname: Goulart
authors.forename: Daniel
authors.initials: D
authors.lastname: Ferreira Costa
authors.forename: Elaine Maria
authors.initials: EM
authors.lastname: de Souza-Fagundes
authors.forename: Dawidson Assis
authors.initials: DA
authors.lastname: Gomes
authors.forename: Lucas Antônio Miranda
authors.initials: LA
authors.lastname: Ferreira
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D004338:Drug Combinations; D005260:Female; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008055:Lipids / Q000737:chemistry; D061986:MCF-7 Cells; D049329:Nanostructures; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004338:Drug Combinations; D056572:Histone Deacetylase Inhibitors; D008055:Lipids; D014280:Triglycerides; D014212:Tretinoin; C005830:tributyrin
keywords: all-trans retinoic acid; cancer; cytotoxicity.; histone deacetylase inhibitors; nanostructured lipid carriers; tributyrin