Development and Evaluation of a Self-Nanoemulsifying Drug Delivery System for Sinapic Acid with Improved Antiviral Efficacy against SARS-CoV-2

This study aimed to develop a self-nanoemulsifying drug delivery system (SNE) for sinapic acid (SA) to improve its solubility and antiviral activity. Optimal components for the SA-SNE formulation were selected, including Labrafil as the oil, Cremophor EL as the surfactant, and Transcutol as the co-surfactant. The formulation was optimized using surface response design, and the optimized SA-SNE formulation exhibited a small globule size of 83.6 nm, high solubility up to 127.1 ± 3.3, and a 100% transmittance. In vitro release studies demonstrated rapid and high SA release from the formulation. Pharmacokinetic analysis showed improved bioavailability by 2.43 times, and the optimized SA-SNE formulation exhibited potent antiviral activity against SARS-CoV-2. The developed SA-SNE formulation can enhance SA’s therapeutic efficacy by improving its solubility, bioavailability, and antiviral activity. Further in silico, modeling, and Gaussian accelerated molecular dynamics (GaMD)-based studies revealed that SA could interact with and inhibit the viral main protease (M^pro). This research contributes to developing effective drug delivery systems for poorly soluble drugs like SA, opening new possibilities for their application via nebulization in SARS-CoV-2 therapy.

2. Materials and Methods

2.1. Screening of Components for SA-SNE Development

The equilibrium solubility of SA was studied in various oils, surfactants, and cosurfactants. Oils of different saturation degrees (medium- or long-chain triglycerides) were utilized to create an SNE to test their solubilization and nano-emulsification ability. The oil with the highest ability to solubilize SA was chosen due to its significant impact on drug solubilization ability and absorption. The tested oils included Labrafil, Capryol-90, Labrafac, olive oil, anise oil, almond oil, soybean oil, and corn oil. The screened surfactants were hydrophilic non-ionic surfactants (Cremophor El, Tween 20, and Tween 80); they have high HLB values and low oral toxicity. Labrasol, Transcutol, PEG 400, and propylene glycol were the screened cosurfactants. An isothermal method previously reported in the literature [15] was utilized for the solubility determination. In brief, 300 mg of SA was added to 1 mL of each component in screw-capped glass vials and mixed using a vortex mixer. The mixtures were then transferred to a thermodynamic water bath shaker (JULABO™, Julabo Labortechnik GMBH, Seelbach, Germany) for continuous shaking at a speed of 100 rpm at room temperature for three days, followed by centrifugation at 4000 rpm for 25 min. SA concentration was measured spectrophotometrically at 322 nm after the supernatant was diluted with methanol using a magnetic stirrer at 500 rpm for 2 min at room temperature [28]. The results of this study provide important insights into the solubility of SA in various oils, surfactants, and cosurfactants, which is crucial for the formulation of SA in a self-nanoemulsifying dosage form.

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Alhadrami, H.A.; El-Din, A.S.G.S.; Hassan, H.M.; Sayed, A.M.; Alhadrami, A.H.; Rateb, M.E.; Naguib, D.M. Development and Evaluation of a Self-Nanoemulsifying Drug Delivery System for Sinapic Acid with Improved Antiviral Efficacy against SARS-CoV-2. Pharmaceutics 2023, 15, 2531. https://doi.org/10.3390/pharmaceutics15112531

excipients formulation