Development of PLGA nanoparticles loaded with clofazimine for oral delivery: Assessment of formulation variables and intestinal permeability

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

Autores

Chaves, LL (Autor) Outra; Costa Lima, SAC (Autor) Outra; Vieira, ACC (Autor) Outra; Barreiros, L (Autor) Outra; Marcela A Segundo (Autor) FFUP; Ferreira, DC (Autor) FFUP; Sarmento, B (Autor) Outra; Salette Reis (Autor) FFUP

Revista

Título: European Journal of Pharmaceutical Sciences

Vol. 112

Páginas: 28-37

ISSN: 0928-0987

Editora: Elsevier

Indexação

ISI Web of Knowledge - 6 Citações

Scopus - 18 Citações

Outras Informações

ID Authenticus: P-00N-7DW

DOI: 10.1016/j.ejps.2017.11.004

Abstract (EN): The use of polymeric nanoparticles as delivery systems is a promising tool to overcome drawbacks related to low aqueous solubility of drugs, which limit their in vivo bioavailability. The aim of this study was to decrease clofazimine (CLZ) toxicity using experimental design to formulate CLZ loaded in PLGA nanoparticles (NPs-CLZ) through a Plackett-Burman design (PBD). A screening PBD was constructed with twelve formulations involving six variables among process and formulation parameters and the selected responses were particle size, polydispersity index (PDI), association efficiency (AE) and drug loading (DL). The formulation was achieved based on the desirability tool, and the obtained NPs-CLZ formulation was characterized regarding morphology, physicochemical properties, in vitro release and cellular studies. Particle size, PDI, AE and DL were found to be 211 +/- 3 nm, 0.211 +/- 0.009, 70 +/- 5% and 12 +/- 1%, respectively. Physicochemical studies confirmed the absence of chemical interactions between CLZ and other nanoparticles constituents and the amorphous state of CLZ, while morphological analysis revealed the spherical shape of the particles. In vitro release profile of CLZ from NPs-PLGA showed a slow pattern of drug release. Cell viability studies towards intestinal cells revealed that NPs-CLZ did not show CLZ toxicity on Caco-2 and HT29-MTX cells compared to free CLZ solutions. Moreover, CLZ could permeate Caco-2 monolayers substantially at the end of 8 h. It can be concluded that the proposed NPs-CLZ represent a promising platform to the oral delivery of CLZ as they were able to decrease its intrinsic toxicity, with improved absorption.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10