A new medium-throughput screening design approach for the development of hydroxymethylnitrofurazone (NFOH) nanostructured lipid carrier for treating leishmaniasis

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2020-09, Vol.193, p.111097, Article 111097
• Main Authors: de Souza, Aline, Yukuyama, Megumi Nishitani, Barbosa, Eduardo José, Monteiro, Lis Marie, Faloppa, Ana Cristina Breithaupt, Calixto, Leandro Augusto, de Barros Araújo, Gabriel Lima, Fotaki, Nikoletta, Löbenberg, Raimar, Bou-Chacra, Nádia Araci
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Drug Carriers - chemistry; Drug delivery system(s); Drug Design; Drug Evaluation, Preclinical; Hydroxymethylnitrofurazone; Leishmaniasis; Leishmaniasis - drug therapy; Lipid-based formulation(s); Lipids - chemistry; Molecular Structure; Nanoparticle(s); Nanostructured lipid carrier; Nanostructures - chemistry; Nitrofurazone - administration & dosage; Nitrofurazone - analogs & derivatives; Nitrofurazone - blood; Nitrofurazone - therapeutic use; Particle Size; Rats; Surface Properties
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2020.111097

[Display omitted] •Developing NLC with NFOH for treating leishmaniasis.•Using design space for development of NLC.•Selecting liquid and solid lipids using different tools.•Determination of NFOH in plasma rat after oral administration.•The novel NLC-NFOH has potential to treat leishmaniasis orally. Hydroxymethilnitrofurazone (NFOH) is a nitrofurazone derivative and has potential use in treating leishmaniasis. However, due to low water solubility and bioavailability, NFOH has failed in in vivo tests. Nanostructured lipid carrier (NLC) is an alternative to overcome these limitations by improving pharmacokinetics and modifying drug delivery. This work is focused on developing a novel NFOH-loaded NLC (NLC-NFOH) using a D-optimal mixture statistical design and high-pressure homogenization, for oral administration to treat leishmaniasis. The optimized NLC-NFOH consisted of Mygliol® 840, Gelucire® 50/13, and Precirol® ATO 5 as lipids. These lipids were selected using a rapid methodology Technobis Crystal 16 T M, microscopy, and DSC. Different tools for selecting lipids provided relevant scientific knowledge for the development of the NLC. NLC-NFOH presented a z-average of 198.6 ± 5.4 nm, PDI of 0.11 ± 0.01, and zeta potential of -13.7 ± 0.7 mV. A preliminary in vivo assay was performed by oral administration of NLC-NFOH (2.8 mg/kg) in one healthy male Wistar rat (341 g) by gavage. Blood from the carotid vein was collected, and the sample was analyzed by HPLC. The plasma concentration of NFOH after 5 h of oral administration was 0.22 μg/mL. This same concentration was previously found using free NFOH in the DMSO solution (200 mg/kg), which is an almost 100-fold higher dose. This study allowed a design space development approach of the first NLC-NFOH with the potential to treat leishmaniasis orally.