**1. Introduction**

Inverse bicontinuous liquid crystalline nanoparticles, termed cubosomes, have advantageous properties that may be suitable for the delivery of bioactive compounds to the small intestine. Amphiphilic lipids such as the monoglyceride monoolein can selfassemble in water to produce dispersions of cubosomes. The basic structure of a cubosome is a honeycomb-like structure with two non-intersecting internal aqueous channels separated by lipid bilayers. The internal hydrophilic (aqueous) areas are separated by lipid bilayers that are twisted into a tightly packed three-dimensional honeycomb structure that has a high internal surface area to volume. Within this structure, encapsulation of diverse hydrophilic, hydrophobic and amphiphilic compounds of small to large molecular weights, such as proteins, peptides, amino acids and nucleic acids, is possible [1]. Within cubosomes, hydrophobic molecules can be located within the lipid bilayers, hydrophilic components in the aqueous channels or around the polar head of the lipid, and amphiphilic molecules can be located at the lipid–water interface. This structure generally maintains the efficacy—stability of actives (vitamins and proteins) without adverse effects

**Citation:** Diep, T.T.; Yoo, M.J.Y.; Rush, E. Tamarillo Polyphenols Encapsulated-Cubosome: Formation, Characterization, Stability during Digestion and Application in Yoghurt. *Antioxidants* **2022**, *11*, 520. https:// doi.org/10.3390/antiox11030520

Academic Editors: Li Liang and Hao Cheng

Received: 8 February 2022 Accepted: 7 March 2022 Published: 8 March 2022

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on the recipient [2]. Both polar and non-polar compounds can be solubilized in the water channel and the bilayers, respectively; therefore, both can be loaded into these particles. According to Meikle et al. [3], cubosomes are relatively non-toxic, stable over a broad range of biologically relevant environmental conditions, and can be formulated using a wide array of lipids and stabilizers. Their size, surface charge, and bilayer structure can be tuned through adjustments in their composition. Moreover, previous studies have demonstrated the ability of cubosomes to deliver drugs to both the eukaryotic and prokaryotic cells [4–8] found in the human digestive system. Cubosome encapsulation has been used to deliver quercetin in vitro [9] and curcumin to the skin [10] and demonstrated improved solubility and availability with an entrapment of 84% and 82%, respectively. Improved anti-inflammatory/antioxidant effects and controlled diffusion of encapsulated curcumin through the skin were observed [10]. Cubosome encapsulated has also enhanced the stability and antibacterial activity of curcumin [11]. Another study had reported successful encapsulation of both piperine and curcumin in the interior of the cubosome particles [12].

Tamarillo (*Solanum betaceum* Cav.), a common fruit of New Zealand, is a good source of polyphenols compounds including anthocyanins, hydroxy benzoic acids, hydroxycinnamic acids, flavonols, flavanols and flavonol glycosides. The main polyphenols in the dried pulp of Laird's Large tamarillo cultivar were identified in our previous study [13] as delphinidin rutinoside (255 mg/100 g), pelargonidin rutinoside (201 mg/100 g DW), chlorogenic acid (66 mg/100 g), kaempferol rutinoside (50 mg/100 g) and cyanidin rutinoside (26 mg/100 g). These polyphenols are strong antioxidants possessing many potential health benefits such as preventing lipid oxidation and are associated with reduced risk for certain cancers, cardiovascular diseases and type 2 diabetes mellitus [14]. Tamarillo fruit therefore has the potential to be an ingredient in functional food products [15]. Evaluation of the stability of polyphenol compounds is important as these compounds are often degraded by oxidation during digestion, resulting in reduced biological activity [16]. For example, anthocyanins, present in high amounts in the nutrient-dense tamarillo, are oxidized into quinones, reducing the biological power of these molecules during digestion [16]. To overcome this obstacle, new generation–functional foods often use encapsulation technologies to protect polyphenols from degradation as well as maintain their bioavailability [16].

This study aimed to investigate the morphology, entrapment efficiency, and particle size of cubosome-encapsulated tamarillo extract (CUBTAM) and test the stability and antioxidant activity and release of the CUBTAM before and after in vitro digestion. In vitro digestion of yoghurt fortified with CUBTAM was similarly investigated for the stability and release of polyphenol compounds.
