The therapeutic properties of clove oil are well known, however, the pungent nature, chemical instability, and low water solubility impose limitations in harnessing its potential. Nanoemulsion of clove oil (CON) was prepared to overcome the above constraints. The non-ionic surfactants Tween 20, 40, and 80 with hydrophile lipophile balance (HLB) of 16.7, 15.6, and 15, respectively, were used to stabilize CON. The creaming index of CON prepared with Tween 20, 40, and 80 was 22.75, 17.5, and 1.5%, respectively, after 8 days of storage at room temperature. Tween 20 and 40 produced particles >300 nm while Tween 80 produced 150 nm. Transmission electron microscopic image of spray-dried CON (with Tween 80) showed particles in the range of 150-190 nm. The in vitro release studies showed 76 and 42% cumulative release of CON and native clove oil (NC), respectively, at pH 7.4. The cellular toxicity of CON was significantly reduced by fourfold compared to NC at a concentration of 60 μg/ml when tested on CaCO 2 cells. Similarly, hemolytic activity on red blood cells revealed less than 10% hemolysis. In addition, CON also exhibited higher in-vitro antioxidant compared to NC as shown by 1, 1-diphenylpicrylhydrazyl and 2,2 0-azino-di-[3-ethylbenzthiazoline sulfonate (6)] (ABTS) radical scavenging activity. Practical application: The study highlights the development of clove oil nanoemulsion using cost-effective, commercially important polysaccharide (maltodextrin) and surfactant for increased bioactivity. The spray-dried nanoparticle showed high retention (95%) of oil and small particle size even after 1 month of storage at room temperature. The biological studies signify the compatibility of nanoparticle for its nutraceutical applications because of its low cytotoxicity (fourfold reduction), hemolytic activity, and high anti-oxidant property. The clove oil nanoparticles can replace the clove oil/microencapsulated particles in food product development due to their high water dispersibility and loading content (25% on dry weight basis). 1 | INTRODUCTION Clove oil, an essential oil extracted from the spice Syzigum aromaticaum, is known for its therapeutic properties such as antioxi

The therapeutic properties of clove oil is known for centuries, however, the pungent nature, chemical instability and low water solubility impose limitations in harnessing its therapeutic potential. Hence, nanoencapsulation of clove oil was performed to overcome the above constraints and control its in-vitro release. The stability of nanoemulsion depends on various factors where the surfactant and its hydrophile/lipofile balance (HLB) play a key role. The non-ionic surfactants Tween 20, 40 and 80 with HLB of 16.7, 15.6 and 15, respectively, were used to study the stability of clove oil nanoemulsion (CON). The creaming index of CON prepared with Tween 20, 40 and 80 was 22.75 and 17.5 and 1.5%, respectively, after 8 days of storage at room temperature. Tween 20 and 40 produced particles > 300 nm while Tween 80 resulted in particles of size ∼150 nm. Transmission electron microscopic image of spray dried CON prepared with Tween 80 showed particle size in the range 150-190 nm after one month of storage at room temperature. The in vitro release studies showed 76% and 42% cumulative release of CON and native clove oil (NC), respectively at pH 7.4. The cellular toxicity of CON was significantly reduced by four fold compared to NC at a concentration of 60 µg/mL when tested on Caco2 cells. Similarly, haemolytic activity on red blood cells revealed less than 10% haemolysis signifying the compatibility of CON for its nutraceutical applications. In addition, CON also exhibited higher in-vitro antioxidant compared to NC as shown by DPPH and ABTS radical scavenging activity. Collectively, we have developed a unique method for NC nanoencapsulation using cost effective polysaccharide (maltodextrin) and surfactant for stabilizing the nanoemulsion for increased bioactivity.