Transdermal cumin essential oil nanoemulsions with potent antioxidant and hepatoprotective activities: In-vitro and in-vivo evaluation
Introduction
Cumin (Cuminum cyminum L.) is an annual herb from Apiaceae family [1]. The spice, C. cyminum (green cumin), is cultivated in Pakistan-India subcontinent, Iran, Egypt, Turkey, North Africa, and Asia [2]. Cumin seeds are used as a spice for their special aromatic effect. The proximate analysis of the seeds reveals that they contain fixed oil (approximately 10%), other elements, and volatile oils (1.5%) [3]. Rebey et al. [4] studied cumin seeds and reported their good content of phenolic compounds which show considerable radical scavenging activity. Ninfali et al. [5] reported that cumin had a significant antioxidant capacity. In general there are two categories of antioxidants; natural and synthetic. Naturally occurring antioxidants are preferred to synthetic ones, which are restricted to their carcinogenicity and toxicity [6]. Naturally occurring antioxidants have the ability to reduce oxidative damage associated with many diseases including cancer, cardiovascular diseases, cataract, arthritis, diabetes etc. [7], [8]. The plant sources are known to contain various biomolecules and phenolics which may vary in the mechanism of action or may work in synergetic manner [9].
Transdermal drug delivery represents the successful and innovative area of research in drug delivery and known to enhance therapeutic efficacy with many advantages over the oral route of administration [10], [11], [12], [13], [14], [15], it avoids hepatic metabolism, the administration is easier and more convenient for patients and there is the possibility of immediate withdrawal of the treatment if necessary [16]. Only a few molecules can be administered transdermally, because of the strong barrier nature of the stratum corneum [17]. Many promising new or existing drugs need to be formulated with smart drug delivery systems to make them acceptable for the treatment of patients [18].
Nanoemulsions have droplet size between 20 and 200 nm that appear transparent or translucent to the naked eyes [19]. Because of their small droplet size, nanoemulsions can offer high thermodynamic stability against aggregation, flocculation, coalescence, and Ostwald ripening. Pharmaceutical phytochemicals can be incorporated into the nanoemulsions and transported through the cell membrane [20]. Nanoemulsions can be used as a vehicle for the transport of pharmaceutical phytochemicals through the stratum corneum barrier in skin-care products because of their stability and rapid permeation properties [21]. Furthermore, nanoemulsions have been described as drug delivery systems and as media to overcome instability to enhance the bioavailability of nutraceuticals [22]. For these reasons, nanoemulsions have increasing interest in food, cosmetic, and pharmaceutical industries [23].
The objective of this work is to encapsulate cumin seed essential oil in nanoemulsions intended for transdermal delivery to provide effective and long-acting systemic antioxidant as well as hepatoprotective effects.
Section snippets
Chemicals
Cumin seed essential oil (CEO) was kindly donated by KATO Aromatic Co., Cairo, Egypt. Briefly, samples of dried cumin seeds (C. cyminum L.) were crushed and ground using a grinder. Finely powdered cumin seeds were covered with sufficient water in a round bottom flask and subjected to hydrodistillation in a modified Likens and Nickerson apparatus which allowed the distillation and simultaneous extraction of the volatile oil in an organic solvent (n-pentane). The n-pentane layer was collected and
Construction of pseudo-ternary phase diagrams
Phase diagrams are constructed to elucidate the relationship between the ratio of components of NEs and their behavior. The oil phase investigated is formed of Capryol™ 90 or oleic acid, Smix; Tween20/ethanol along with distilled water. Six phase diagrams are plotted representing the 2 used oils and 3 Smix ratios; 1:1, 2:1, and 3:1 (Fig. 1A & B). The large NE existence zone in all the investigated phase diagrams encouraged the authors to select a NE system from each, to proceed with further
Conclusion
Six CEO NE formulations are dispensed from 6 phase diagrams employing Capryol™ 90 and oleic acid as oil phases along with Tween 20/ethanol; Smix, and double distilled water. The formulations show good phenolic compounds (EE%). Four formulations; S2, S3, S5, and S6 show appreciably high permeation after 6 h. S5 and S6 show higher zeta potential values inferring good stability. The four formulations reveal appreciably higher in-vitro antioxidant efficacy compared to CEO per se, using DPPH-assay
Declaration of interest
The authors report no declarations of interest.
Acknowledgments
The authors extend their appreciation to the Project's Sector at the National Research Centre, Egypt for funding this work through the research group project fund no. 10070107.
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