Red fruit (Pandanus conoideus) is an endemic fruit that grows in the Papua region, especially in the mountainous areas of Jayawijaya, Ayamaru Sorong, Timika, Nabire, Manokwari, Jayapura, and Papua New Guinea [1,2]. Traditionally, people use this fruit as a food supplement, skin care cosmetic ingredients, and a substitute for cooking oil. This red fruit contains lipids, sodium, vitamin C, β-carotene, β-cryptoxanthin, phenolic compounds, and α-tocopherol. β-Carotene is a potent antioxidant that may benefit the brain, skin, lung, and eye health [1].

β-Carotene is widely used in manufacturing food, medicine, and cosmetics. The β-carotene content in this fruit can become a source of vitamin A in the body, maintaining eye health and improving overall skin health [3,4]. β-Carotene can also help reduce high blood pressure by slowing the buildup of plaques in the arteries. Previous studies have shown that β-carotene can also prevent and inhibit several types of cancer cells [2,4]. In cosmetics, β-carotene can be found in hand washes and creams to prevent irritation. When β-carotene is topically applied, it penetrates the deeper layers of the skin and helps to repair ultraviolet (UV) light damage and free radicals. In addition, β-carotene can provide a healthy and natural color to the skin, which makes the skin look brighter and more radiant. β-Carotene experiments on the skin have been studied in vitro model tests, and the results showed that β-carotene revealed a protective effect against skin cancer caused by chemicals and UV-irritation [5,6].

Although β-carotene can provide significant health benefits, designing the delivery system of β-carotene is essential. Different application sites of this substance can cause other effects too. When consumed orally, β-carotene is absorbed by the body and carried throughout the body, including the skin [5,6]. However, not all the β-carotene consumed will reach the skin because most of the β-carotene that enters the body is used for other purposes, such as strengthening the immune system or improving eye health. However, intravenously injecting β-carotene is also hard to consider because of the unpractical application and complicated manufacturing process [7]. In this research, we have focused on localizing the effect of β-carotene in the skin. β-Carotene applied topically to the skin can be directly absorbed by skin cells and provide direct benefits, such as increasing melanin production and protecting the skin from UV light damage.

Several pharmaceutical preparations are used for topical drug delivery systems, including topical liquid, solid powder, ointment, cream, and gel. Among the dosage forms, a gel is the newest dosage form, superior to other dosage forms in terms of ease of use and patient acceptability. Gels also offer faster drug release when compared to other topical dosage forms [8]. However, gels have some limitations, especially in delivering hydrophobic substances. To overcome this limitation, emulgel is the primary option that can be considered.

Emulgel is simply a mixture of gels and emulsions, both oil in water (O/W) and water in oil (W/O) types. Compared to creams, topical emulsion or emulgel is a better choice regarding patient comfort because it is non-sticky and non-greasy. In addition, emulgel, particularly nanoemulgel, can easily penetrate the skin due to its small droplet size and significantly enhance drug loading. Several studies have shown successful topical delivery of drugs using nanoemulgel [9,10]. Recently, microneedles have been attractively and widely used to improve transdermal drug delivery. There are many types of microneedles, including solid microneedles (SMN), coated microneedles, dissolving microneedles, hollow microneedles, and hydrogel-forming microneedles. Among them, SMN can improve drug delivery into the skin because of its ability to penetrate the stratum corneum, which consists of dead skin cells [11]. SMN has been proven practical, safe, and painless and can increase drug absorption into the skin [12]. SMN has been previously used with positive outcomes for drug delivery through the skin [13].

In this study, nanoemulgel with thermosensitive properties was prepared in liquid form at room temperature, making it easy to apply on the skin, but it would stiffen at body temperature, called sol-gel transition [14]. In addition, thermosensitive gels can extend the drug's residence time on the target site, increase the local drug concentration, and improve the bioavailability of the drug [15].

The objectives of this study were to develop a thermosensitive nanoemulgel loading Papuan red fruit (Pandanus conoideus) oil combined with SMN and characterize for effective release of β-carotene in both ex vivo and in vivo from the formulation.