Design of multifunctional nanostructured lipid carriers enriched with α-tocopherol using vegetable oils
Graphical abstract
Introduction
There is a growing demand for innovative natural products to address consumers’ needs of healthy appearance and well-being. Cosmetic manufacturers are focusing their efforts in the development of eco-friendly cosmetics based on vegetable oils as raw materials, since they are abundant renewable resources most commonly extracted from various parts of plants (Badea et al., 2015; Balboa et al., 2014). Vegetable oils are a combination of triglycerides of higher saturated and unsaturated fatty acids. Due to their beneficial influence on skin these type of oils are becoming most commonly used as components of cosmetic products (Zielińska and Nowak, 2014). Antioxidant properties have been attributed to vegetable oils which can provide skin protection against reactive oxygen species (ROS) (Dhavamani et al., 2014; Tehranifar et al., 2011) synergistically improving the photoprotective properties of sunscreens (Dario et al., 2018). Moreover, oils can prevent water loss through the skin and also present anti-carcinogenic and anti-inflammatory biological actions (Cicerale et al., 2012). Topical supplementation with antioxidants is considered as one of the most promising strategies to prevent or treat skin aging. Most skin care formulations claiming anti-aging effects are based on exogenous antioxidants such as vitamins, polyphenols, and flavonoids that cannot be synthesized by our body (Montenegro, 2014). α-Tocopherol (TOC) is one of the most active lipophilic antioxidant in biological membranes demonstrating a very important role in protecting skin and other organs. This fat-soluble antioxidant can effectively scavenge lipid peroxyl radicals, act as a synergist with other antioxidants and presents a moisturizing effect by limiting trans-epidermal water loss (Byun et al., 2011; Yenilmez and Yazan, 2010). However, TOC is present in limited quantities, humans cannot synthesize it and it is readily depleted by UV radiation and other oxidative stresses such as ozone (de Carvalho et al., 2013; Nada et al., 2014). Given its importance, TOC is widely used in the formulation of several cosmetic and daily care products and there is a commercially available nanoemulsion, TOCOSOL™, composed of TOC as oil phase, TPGS and Poloxamer 407 as surfactants for paclitaxel intra-venous delivery (Constantinides et al., 2000; Feng and Mumper, 2013; Nada et al., 2014). The great majority of antioxidants, including TOC, that are presently used in skin care formulations show unfavorable physicochemical properties such as excessive lipophilicity or hydrophilicity, chemical instability and poor skin penetration that actively limit their effectiveness after topical application (Montenegro, 2014). One good strategy to reduce these effects is the design of nanomaterials with an intrinsic multifunctional character based on its excipients to encapsulate these antioxidant substances. Therefore, different lipid nanocarriers such as liposomes, niosomes, microemulsions and nanoparticles have been widely investigated as delivery systems for antioxidants to improve their beneficial effects in the treatment of skin aging (Nada et al., 2014). The main advantages of lipid nanocarriers over conventional passive delivery are good biocompatibility, increased surface area, higher solubility, improved stability, good production scalability, controlled release, avoidance of organic solvents in the preparation process and wide potential application spectrum (Vinardell and Mitjans, 2015). Solid lipid nanoparticles (SLNs) are often referred in literature as the first generation of lipid nanocarriers (Attama et al., 2012; Müller et al., 2002). In order to overcome some difficulties with SLNs regarding its inherent low incorporation rate due to the crystalline structure of the solid lipid, nanostructured lipid carriers (NLCs) were introduced as the second generation of solid lipid nanoparticles (Aditya et al., 2014; Weber et al., 2014). NLCs are submicron particles, usually with spherical shape and mean diameters ranging between 50 and 500 nm, composed of a mixture of solid and liquid lipids (oils) dispersed in an aqueous medium and stabilized by an outer shell of surfactants (Niculae et al., 2014; Puri, 2010). The oil incorporation in the solid matrix allows the formation of an overall amorphous nanostructure with many imperfections within its matrix, providing NLCs with higher drug capacity and a lesser degree of drug expulsion during storage then SLNs (Fang et al., 2013; Pinto et al., 2014). These lipid nanocarriers are one of the most effective encapsulation technologies developed in the field of nanotechnology with a wide range of applications in the cosmetics, food and pharmaceutical industries (Zheng et al., 2013). Moreover, they are safe for human use and biodegradable carriers due to their generally recognized as safe (GRAS) ingredients (Müller et al., 2000). The physicochemical properties of NLCs are influenced by a number of factors, including the type of used oil and surfactant (Badea et al., 2015). There are several reports focusing a certain bioactive-loaded NLC but only few studies addressed the influence of different lipids and surfactants on the formulation of NLC and their properties (Badea et al., 2015; Lacatusu et al., 2014; Niculae et al., 2014). The novelty of the present work consist on the production of new formulations of NLC based on the use of bioactive ingredients such as the selected four vegetable oils, and α-tocopherol as model lipophilic drug to be encapsulated. The present study aimed to investigate the effects of different vegetable oils and surfactants on the design of multifunctional NLCs formulations enriched with TOC as a model antioxidant excipient. SF, SA, OV and CO oils were chosen as liquid lipids not only for their physicochemical properties but also for their intrinsic multifunctional character as moisturizers, antioxidant agents and anti-carcinogenic and anti-inflammatory biological actions. Also, vegetable oil NLCs were formulated using four non-ionic surfactants (Tween 80, Poloxamer 188, Span 60 and Span 80), to further improve the particles size and stability. The miniemulsions methodology (Landfester, 2003), a simple solvent free and low energy method, was used for preparing the NLCs. Additionally, vegetable oil NLCs were characterized in terms of particle size and zeta potential, crystallinity and melting behavior, and morphology. Additionally, entrapment efficiency, loading capacity, release profile, stability studies and in vitro antioxidant activity were also evaluated.
Section snippets
Materials
Solid lipids: lauric acid (≥98%); myristic acid (Sigma Grade, ≥99%); palmitic acid (≥99%) and stearic acid (≥95%) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Liquid oils: Sunflower (SF) oil, (Fula, Portugal) and Olive (OV) oil, (Gallo, Portugal) were food grade commercial products; Sweed almond (SA) oil, (Well's, Portugal) was a cosmetic grade product and Coconut (CO) oil, with analytical grade (Supelco, USA). Surfactants: Tween 80, (polyoxyethylene sorbitan monooleate, HLB 15.0)
Influence of vegetable oil type and proportion
The effects of the vegetable oil composition and proportion in the preparation of NLCs using Tween 80 as a surfactant and myristic acid (C14:0) as a solid lipid on the particle size and physical stability were evaluated. The percentage of lipid phase (blend of solid lipid and liquid oil) on the miniemulsions was kept constant (Table 1), while the solid lipid, wt%: vegetable oil, wt% ratio in the lipid phase varied. The mean particle size, the PdI and zeta potential of the lipid nanocarriers are
Conclusions
Four vegetable oils, presenting inherent beneficial bioactive properties were selected and successfully applied in new formulations of multifunctional free NLCs and TOC-NLCs. From the present study, it was demonstrated that the particle size, the size distribution and the surface charge of the lipid nanoparticles are significantly influenced by the composition of the lipids core and by the type of used surfactant. NLC formulations with different lipid matrices were obtained by the miniemulsion
Conflict of interest
There is no conflict of interest.
Acknowledgments
Funding received by iBB-Institute for Bioengineering and Biosciences from FCT (UID/BIO/04565/2013) and from Programa Operacional Regional de Lisboa 2020 (Project N. 007317) is acknowledged.
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