Optimized Chitosan-Based Nanoemulsion Improves Luteolin Release

Camila Diedrich; Isabella C Zittlau; Najeh M Khalil; Adam F G Leontowich; Rilton A de Freitas; Ildiko Badea; Rubiana M Mainardes

doi:10.3390/pharmaceutics15061592

Optimized Chitosan-Based Nanoemulsion Improves Luteolin Release

Pharmaceutics. 2023 May 25;15(6):1592. doi: 10.3390/pharmaceutics15061592.

Authors

Camila Diedrich¹, Isabella C Zittlau¹, Najeh M Khalil¹, Adam F G Leontowich², Rilton A de Freitas³, Ildiko Badea⁴, Rubiana M Mainardes¹

Affiliations

¹ Pharmaceutical Nanotechnology Laboratory, Universidade Estadual do Centro-Oeste, Guarapuava 85040-167, Brazil.
² Canadian Light Source, Saskatoon, SK S7N 2V3, Canada.
³ Biopol, Chemistry Department, Federal University of Parana, Curitiba 81531-980, Brazil.
⁴ Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.

Abstract

Luteolin (LUT) is a flavonoid found in several edible and medicinal plants. It is recognized for its biological activities such as antioxidant, anti-inflammatory, neuroprotective, and antitumor effects. However, the limited water solubility of LUT leads to poor absorption after oral administration. Nanoencapsulation may improve the solubility of LUT. Nanoemulsions (NE) were selected for the encapsulation of LUT due to their biodegradability, stability, and ability to control drug release. In this work, chitosan (Ch)-based NE was developed to encapsulate luteolin (NECh-LUT). A 2³ factorial design was built to obtain a formulation with optimized amounts of oil, water, and surfactants. NECh-LUT showed a mean diameter of 67.5 nm, polydispersity index 0.174, zeta potential of +12.8 mV, and encapsulation efficiency of 85.49%. Transmission electron microscopy revealed spherical shape and rheological analysis verified the Newtonian behavior of NECh-LUT. SAXS technique confirmed the bimodal characteristic of NECh-LUT, while stability analysis confirmed NECh-LUT stability when stored at room temperature for up to 30 days. Finally, in vitro release studies showed LUT controlled release up to 72 h, indicating the promising potential of NECh-LUT to be used as novel therapeutic option to treat several disorders.

Keywords: chitosan; drug release; optimization; response surface methodology; stability.

Grants and funding

This study was financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001 and PDSE scholarship—88881.622891/2021-01, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 316887/2021-8, Financiadora de Estudos e Projetos (Finep), the Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-03689) and the College of Pharmacy and Nutrition, University of Saskatchewan. SAXS measurements described in this paper were performed at the Canadian Light Source, a national research facility of the University of Saskatchewan, which is supported by the Canada Foundation for Innovation (CFI), the Natural Sciences and Engineering Research Council (NSERC), the National Research Council (NRC), the Canadian Institutes of Health Research (CIHR), the Government of Saskatchewan, and the University of Saskatchewan.