Investigation and Evaluation of Dually Loaded Niosomes Containing Crocin and Omega-3 by Heating & Bubble Method

مجله پژوهشهای علوم و صنایع غذایی ایران

Volume 21, Issue 2 - Serial Number 92, May and June 2025, Pages 217-234   

Document Type: Research Article

DOI: 10.22067/ifstrj.2024.88094.1367

Authors

Parisa Mardani¹; Ghadir Rajabzadeh^{* 1}; Bijan Malaekeh-Nikouei²; Aram Bostan¹

¹Department of Food Nanotechnology, Research Institute of Food Science and Technology (RIFST), Mashhad, Iran

²Pharmaceutical Technology Institue, Mashhad University of Medical Science, Mashhad, Iran

Abstract

Introduction
The majority of pharmaceuticals and nutraceuticals are encapsulated in various delivery vehicles in order to avoid some restrictions. This is mainly due to the molecules' physicochemical instability in physiological structure and/or their low bioavailability. Food ingredients or bioactive components can be encapsulated inside delivery systems for protection and controlled release. Encapsulated ingredients are protected from unfavorable reactions, such as lipid oxidation and volatile loss during production, storage, and handling.
Materials and Methods
Flaxseed oil was purchased from Barij Essence Pharmaceutical Co., Tehran, Iran. Saffron was bought from Novin Saffron Co., Mashhad, Iran. Cholesterol, span 60 and tween 60 were from Sigma-Aldrich. Phosphate buffered saline, sodium azide, hydrochloric acid, and other chemicals were procured from Merck (Darmstadt, Germany). All other solvents and reagents were provided from Merck Pharmaceutical Co. (Germany) as analyticall grade.
Crocin Extraction
The extraction of crocin from saffron was done based on crystallization method which has been explained by Mohajeri et.al.
Flaxseed Oil Extraction
Flaxseed is one of the richest plant sources of ω-3 fatty acids, alpha-linolenic acid (ALA, C18:3 ω-3). A Soxhlet extraction was carried out on flaxseed powder (20g) using n-hexane for 14 hours at 70°C. After extraction, the sample was concentrated in a rotary evaporator at 40°C .
Niosome Preparation
A surfactant with a HLB number between 3 - 8 is suitable for the co-encapsulation of hydrophobic and hydrophilic substances (Korani et al. 2019. Hence, span 60: tween 60 variable ratios were selected to achieve HLB in this range. Additionally, the ratio of surfactants to Chol was considered variable. The DCP was applied at a constant concentration to enhance noisome stability.
Results and Discussion
Characterization of niosomes
The influence of experimental variables on the particle size, PDI and zeta potential of niosomes prepared by heating and bubble methods was investigated. In order to choose the appropriate ratios of surfactant, the physicochemical characteristics of niosomal particles, including particle size, zeta potential, PdI, and EE have been considered.
Tween 60 is a nonionic surfactant with a large hydrophilic head group and high HLB (14.9). In turn, span 60 has a large hydrophobic moiety (HLB 4.7) and low water solubility. The smaller head groups and longer alkyl chains in surfactant structure have led to larger vesicles. This might be the reason for the larger particle size of H1-H3 and B1-B3, containing higher amount of span 60 compared to other samples.
   The PDI of the prepared samples was found in the range of 0.29 to 0.49. This value was considered to be within the range of sufficient for attaining stable and aggregation resistant systems. However, higher span 60 content showed comparatively a lesser degree of PDI.
   Zeta potential is a respectable index of the quantity of the interaction between colloidal particles. In this work, the prepared niosomes had a zeta potential range of -31 to -48 mV, which was sufficient to maintain niosome stability without aggregation between vesicles. Negative zeta-potential in nonionic surfactant vesicles has been reported.
   Based on the results, B12 and H12 samples with the span: tween ratio of 4:1 and surfactant: Chol ratio of 1:1 formed better niosomes based on particle size, PDI, EE, and zeta potential.
In the optimum conditions, the EE of crocin and ω-3 in heating method were 76% and 32%, and in bubble method they were 73% and 28%, respectively.
Stability of niosomes
The stability of the optimum niosomes prepared by bubble and heating methods were evaluated at 4°±2°C, 25±2°C, and 37°±2°C for 90 days, by means of stability in size, PDI, and EE.             
 Conclusion
 In conclusion, this study revealed that co-encapsulation of omega3 and crocin with niosome led to better stability, slower and more controlled release profile, suggesting a promising drug delivery system.

Keywords

Bubble method; Crocin; Heating method; Niosome; Omega-3

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