Lupeol-loaded PLGA particles conserve anti-topoisomerase activity and decrease the cytotoxicity of lupeol

Triterpenes and steroids constitute a broad class of compounds, with approximately 4000 structures derived from mevalonic acid. Their biosynthesis begins with the condensation of two farnesyl pyrophosphate units to form squalene, which is subsequently converted to 2,3-squalene epoxide and cyclized via two main pathways leading to the triterpenes formation (Sharma et al., 2020). These compounds serve as steroid precursors in both plants and animals (Patil et al., 2018). In plants, they are an essential component of cuticular wax and play defensive roles through antibiotic, fungicidal, and antiprotozoal activities. The structural diversity and biological activity of different classes of pentacyclic triterpenes have supported drug development for therapeutic applications in many areas. Among the most biologically relevant terpenes are the lupanes, such as lupeol, betulinic acid, and botulin (Buszewski et al., 2019; Tamfu et al., 2022).

Lupeol (LP), a phytochemical with the scientific name Lup-(20)29-en-3β-ol, is also known as lupeol, clerodol, fagarsterol, or lupenol. LP is present in various plant species and has been found in white cabbage, pepper, cucumber, tomato, carrot, pea, bitter root, soybean, pumpkin, black tea, fig, strawberry, red grape, mulberry, date palm, and guava. Quantitative studies have shown that LP is present in olive fruit (3 μg / g), mango (1.80 μg / g pulp), aloe leaf (280 μg / g dried leaf), Japanese pear (175 μg / g peel), and ginseng oil (15.2 mg / 100 g oil) (Li and Xiao, 2018). There are numerous studies in which LP possesses several biological properties, including antioxidant, anti-inflammatory (Sánchez-Burgos et al., 2015; Cháirez-Ramírez et al., 2015), anti-arthritic (Song et al., 2022), and antimutagenic activities (Srivastava et al., 2016). It has also been reported that LP can modulate protein kinases, serine proteases, and topoisomerase II, a key target in anticancer therapy (Sánchez-Burgos et al., 2015). Animal studies have shown that LP has inhibitory activity against several cancer types, including prostate cancer, melanoma, and head and neck cancer. Additionally, LP demonstrates antimicrobial, anti-inflammatory, antiproliferative, and antioxidant properties in multiple in vitro and in vivo assays (Liu et al., 2021).

Gastrointestinal digestion represents a barrier for phytochemicals to reach target sites, particularly at effective concentrations (Nolasco et al., 2021). During the digestive process, gastrointestinal proteolytic enzymes and pH fluctuations can inactivate these bioactive compounds or release them from the structural matrix of the plant product (Coelho et al., 2021). Therefore, it is crucial to protect bioactive compounds during digestion and gastrointestinal absorption (Demarco et al., 2022). Therefore, encapsulation is an alternative to maintain the chemical integrity of these molecules. The use of microparticles in medicine includes the use of these structures as supports or barriers by encapsulating drugs (Cháirez-Ramírez et al., 2015). The use of such particles has improved the therapeutic efficacy of many drugs, reducing both the doses required and side effects (Marcillo-Parra et al., 2021). Therefore, this study aimed to develop poly (lactic-co-glycolic acid) (PLGA) particles capable of protecting lupeol (LP) and preserving its biological activity.

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