Squalane

The 5-α-Cholestan-3-ol, heneicosanol, betulinic acid, squalane, and tocopherols (α, β, γ, δ) standards (Purity 99%) were supplied by Sigma-Aldrich SA (St. Louis, MO, USA). N,O-Bis (trimethylsilyl) trifluoroacetamide (BSTFA) containing 1% trimethylchlorosilane (TMCS) was purchased from Supelco (Bellefonte, PA, USA) and used as a silylation reagent. All other chemicals and reagents were of analytical grade and were acquired from local suppliers.

P.a. grade ethyl acetate and n-hexane from Merck (Darmstadt, Germany) and acetone from Honeywell (Seelze, Germany) were used for standards preparation and sample treatment. HPLC grade methanol from Honeywell (Seelze, Germany) and deionised water from a Milli-Q apparatus (Millipore, Milford, MA, USA) were used to prepare mobile phase for HPLC analysis. Ammonium formate was LC–MS grade (Sigma-Aldrich, St. Louis, MO, USA).
Terpene reference standards of α-humulene (96%), limonene (97%), myrcene (>90%), α-pinene (99%), β-pinene (97%), and α-terpinene (95%) were obtained from Sigma-Aldrich (St. Louis, MO, USA).
Cannabinoid reference standards of cannabigerol (CBG, 99%) and cannabidiol (CBD, 99.9%) in solid form were obtained from LGC standards (Teddington, Middlesex, UK). Δ8-tetrahydrocannabinol (Δ8-THC), Δ9-tetrahydrocannabinol (Δ9-THC), cannabichromene (CBC) and cannabinol (CBN) were obtained as solution in methanol (1 mg/mL) from LGC standards as well.
Squalane (96%) was purchased from Sigma-Aldrich (St. Louis, MO, USA) and was applied as internal standard (IS).
Buds of industrial hemp plant (stemless) material of various cultivars were obtained from local hemp growers.

PM was purified from Halobacterium salinarum strain R1 (JMC9409) by a standard procedure^{1 (link)}. Crystals were obtained by the LCP method^{47 (link)} with some modification. Briefly, squalane (Sigma-Aldrich) and trehalose C16 (Dojin) were added to the monoolein-based LCP at final concentrations of 1.0% and 5.0%, respectively. 20 μL of bR solution and 32 μL of the LCP matrix were mixed with two syringes (Hamilton) coupled with a connector^{48 (link)}. Each LCP drop (2 μL) was immersed in 30 μL of 1.8 M Na/K phosphate (pH 5.6) in a microbridge (Hampton Research). The microbridge was located with 500 μL of 2.0−2.5 M Na/K phosphate (pH 5.6) in a 24-well crystallization plate. Crystals were grown to a typical size of 300 × 300 × 40 − 400 × 400 × 50 μm³ after more than 3 months (Supplementary Fig. 1a). The LCP containing matured crystals was equilibrated to 2.5 M Na/K phosphate for ~24 h. The LCP matrix around crystals was removed by washing with squalane oil. The squalane oil was also used as a cryoprotectant. The crystals were picked up with nylon loops and flash cooled with a nitrogen gas stream at 100 K after illumination with white halogen light for ~1 min. The frozen crystals were transferred to liquid nitrogen while avoiding light, and stored in a liquid nitrogen tank.

Plant-derived solanesol was obtained from TCI America. Shark-derived squalene, squalane, and sorbitan trioleate were obtained from Sigma-Aldrich. Napa Valley Naturals (Stonewall Kitchen) grapeseed oil was purchased from a local grocery store. DMPC was obtained from Lipoid. Poloxamer 188, α-tocopherol, and glycerol were purchased from Spectrum Chemical. Polysorbate 80 was obtained from NOF. Buffer components were obtained from J.T.Baker and Fluka. Split, inactivated H5N1 (A/Vietnam/1194/2004) was obtained from the National Institute for Biological Standards and Control (NIBSC). For the SE compositions, terpenoid oils were formulated with a mixture of emulsifiers (DMPC and Poloxamer 188), an antioxidant agent (α-tocopherol), a tonicity agent (glycerol), and a buffer system (25 mM ammonium phosphate, pH 5.8) and processed by high-shear mixing and high-pressure homogenization to generate 4% v/v oil-in-water nanoemulsions^{16 (link)}. For the MF59-like compositions, terpenoid oils were formulated with a mixture of non-ionic surfactants (polysorbate 80 and sorbitan trioleate) and a buffer system (10 mM citrate, pH 6.0), and processed by high-shear mixing and high-pressure homogenization to generate 4% v/v oil-in-water nanoemulsions^{27 (link)}.

Commercial seeds of fenugreek (Trigonella foenum-graecum L.) were purchased from Murciana de Herboristeria (Murcia, Spain) and seeds of red quinoa (Chenopodium quinoa Willd.) were purchased from Hijo de Macario Marcos (Salamanca, Spain). Trizma base, maleic acid, sodium chloride, calcium chloride, HCl, Amano lipase A from Aspergillus niger, pepsin, pancreatin from porcine pancreas, bile salts, phosphatidyl choline from egg yolk, β-sitosterol (≥70%), oleic acid, lysine, 1,3-diolein, 1-oleoyl-rac-glycerol, myo-inositol, d-glucose, quercetin, diosgenin, hederagenin, protocatechuic acid, squalane, and N,O-bis-(trimethylsilyl)trifluoroacetamide (BSTFA) were from Sigma-Aldrich Chemie GmbH (Steinheim, Germany). Sucrose was from Panreac (Barcelona, Spain). Dioscin, protodioscin, 5-pentadecylresorcinol and oleanolic acid were from Cymit Quimica S.L (Barcelona, Spain). Methanol, hexane, 1-butanol, chloroform were from Macron (Gliwice, Poland).

Tetraethyl orthosilicate (TEOS, ≥ 99.0%), 2-amino-2-(hydroxymethyl)-1,3-propanediol (AHMPD, ≥ 99.9%), cetyltrimethylammonium tosylate (CTATos, ≥ 98.0%), ammonium nitrate (NH₄NO₃), ferric chlorid (99%) and squalane (96%) were obtained from Sigma–Aldrich (Lyon, France). Nitric acid 65% (HNO₃) was purchased from Carlo-Erba (Barcelona, Spain). Sodium stearate (98.8%) was obtained from TCI (Tokyo, Japan). Oleic acid (99%) was purchased from Alfa Aesar (Lancashire, UK) while dibenzylether (DBE, 99%) was purchased from Acros Organic (Waltham, Massachusetts, USA).