Overcoming clofazimine intrinsic toxicity: statistical modelling and characterization of solid lipid nanoparticles

• Tipo: Artigo em Revista Científica Internacional
• Data: 2018

Autores

Chaves, LL (Autor) Outra; Lima, S (Autor) Outra; Vieira, ACC (Autor) Outra; Ferreira, DC (Autor) FFUP; Sarmento, B (Autor) Outra; Salette Reis (Autor) FFUP

Revista

Título: Journal of the Royal Society Interface

Vol. 15

Página Final: 20170932

ISSN: 1742-5689

Editora: The Royal Society

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 9 Citações

Outras Informações

ID Authenticus: P-00N-J73

DOI: 10.1098/rsif.2017.0932

Abstract (EN): The aim of this work was to develop solid lipid nanoparticles (SLNs) loaded with clofazimine (CLZ) (SLNs-CLZ) to overcome its intrinsic toxicity and low water solubility, for oral drug delivery. A Box-Behnken design was constructed to unravel the relations between the independent variables in the selected responses. The optimized SLNs-CLZ exhibited the following properties: particle size ca 230 nm, zeta potential of -34.28 mV, association efficiency of 72% and drug loading of 2.4%, which are suitable for oral delivery. Further characterization included Fourier transformed infrared spectroscopy that confirmed the presence of the drug and the absence of chemical interactions. By differential scanning calorimetry was verified the amorphous state of CLZ. The storage stability studies ensured the stability of the systems over a period of 12 weeks at 4 degrees C. In vitro cytotoxicity studies evidenced no effect of both drug-loaded and unloaded SLNs on MKN-28 gastric cells and on intestinal cells, namely Caco-2 and HT29-MTX cells up to 25 mu g ml(-1) in CLZ. Free CLZ solutions exhibited IC50 values of 16 and 20 mu g ml(-1) for Caco-2 and HT29-MTX cells, respectively. It can be concluded that the optimized system, designed considering important variables for the formulation of poorly soluble drugs, represents a promising platform for oral CLZ delivery.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10