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

Author(s)

de Souza, Aline ^[1] ; Yukuyama, Megumi Nishitani ^[1] ; Barbosa, Eduardo Jose ^[1] ; Monteiro, Lis Marie ^[1] ; Breithaupt Faloppa, Ana Cristina ^[2] ; Calixto, Leandro Augusto ^[3] ; de Barros Araujo, Gabriel Lima ^[1] ; Fotaki, Nikoletta ^[4] ; Lobenberg, Raimar ^[5] ; Bou-Chacra, Nadia Araci ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Med Sch, Heart Inst InCor, LIM 11, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Exact & Earth Sci, Diadema, SP - Brazil

^[4] Univ Bath, Dept Pharm & Pharmacol, Bath, Avon - England

^[5] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB - Canada

• Document type: Journal article
• Source: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 193, SEP 2020.
• Web of Science Citations: 0

Abstract

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 (R) 840, Gelucire (R) 50/13, and Precirol (R) 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 mu g/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. (AU)

• FAPESP's process: 17/08332-3 - NANOSTRUCTURED SYSTEMS WITH POTENTIAL APPLICATION IN TREATMENT OF NEGLECTED DISEASES
• Grantee: Nádia Araci Bou-Chacra
• Support Opportunities: Regular Research Grants