The traditional use of plants, both used directly and extracted, for medicinal purposes has existed since ancient times ^[1][2][1,2]. Plants are a source of various phytochemicals and have been used for human health because of their low side effects, low cost, and high acceptance by the general public [3].

Phytochemicals are substances produced by plants (also known as secondary metabolites) that play an important role in traditional medicine. Secondary metabolites have been shown to exhibit various biological activities, which provide a scientific basis for the use of herbs in traditional medicine. They show pharmacological effects that can be used to treat bacterial and fungal infections and even chronic degenerative diseases, such as diabetes and cancer ^[4][5][4,5].

Herbal medicines are increasingly popular throughout the world and have promising potential to provide treatment, maintain and improve health, as well as prevent and treat several diseases because they are considered safe compared to modern conventional medicines and are more economical ^[6][7][6,7]. However, most of these biologically active phytochemical constituents have limitations; namely, their absorption and distribution are low, and the target specificity of phytochemicals is generally low, which results in low bioavailability, resulting in decreased biological activity. In addition, large doses are required to produce the activity of these phytochemical compounds, and also some of these phytochemical compounds are sensitive to acidic conditions and have low stability phytochemical compounds ^{[6][8][9][10][11]}[6,8,9,10,11]. These limits hinder their clinical application.

Puerarin is the main active compound isolated from the roots of Pueraria lobata (Willd.) Ohwi, which has broad pharmacological activity. Puerarin is used for cardiovascular disease, diabetes, osteonecrosis, Parkinson’s disease, Alzheimer’s disease, endometriosis, and cancer [12]. Puerarin has a low solubility in water: 0.46 mg/mL. The maximum solubility of puerarin occurs in a phosphate buffer of pH 7.4 at 7.56 mg/mL ^[13][14][13,14]. The low solubility limits the application of puerarin. In recent years, research on increasing the bioavailability of puerarin has grown rapidly. Various nanotechnology has been investigated to increase the bioavailability of puerarin, one of which is the solid lipid nanoparticle (SLN) carrier system. Compared to puerarin suspension, SLN-puerarin is absorbed rapidly. This is supported by a shorter Tmax. In addition, SLN-puerarin showed more than threefold bioavailability compared to puerarin suspension ^[15][16][15,16].

Nanotechnology-based delivery systems function as drug carriers that can overcome the various limitations that herbal medicines face, including increasing the bioavailability and bioactivity of phytochemicals. The approach using nanotechnology can be a promising innovative technology that is applied to phytochemical constituents, increasing the phytotherapy efficiency of herbal medicines. The development of an efficient and safe drug delivery system is the goal of various researchers. Recent developments in the field of nanotechnology have led to renewed interest in herbal medicinal formulations. Several delivery system approaches, such as phytosomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), polymeric nanoparticles, nanoemulsions, etc., have been proposed. Nanoparticles have been used to modify and improve the pharmacokinetic properties of different drugs, so the nanotechnology approach is expected to increase the bioavailability and bioactivity of herbal medicines ^{[6][10][17][18]}[6,10,17,18].

2. Nanotechnology-Based Drug Delivery System for Phytochemical Compounds

According to the literature, 70% of the active ingredients obtained from plants are hydrophobic [3]. New technology has been used as a strategy to increase the bioavailability/bioactivity of phytochemical compounds. In order to develop new nanotechnology-based therapies, the ability to design suitable formulations for drug delivery is of the utmost importance. Phytochemical delivery is essential for effective disease prevention and treatment. These delivery systems include lipid-based delivery systems and polymer-based delivery systems, which have the potential to increase the bioactivity of phytochemical compounds (Figure 12) ^[19][20][21][22,24,25]. New drug delivery systems based on nanotechnology have been developed for effective herbal drug delivery ^[24][27]. Lipid-based carrier systems (Figure 23) consisting of vesicular systems (liposomes, phytosomes, transfersomes, ethosomes, and niosomes), lipid particulates (SLN and NLC), and nanoemulsions have garnered particular interest for phytochemical delivery aimed at increasing bioactivity and bioavailability, as well as the stability of phytochemical compounds [3]. Vesicular drug delivery systems can be defined as highly ordered assemblies consisting of one or more concentric bilayers formed as a result of self-assembly in the presence of water ^[25][28]. SLN and NLC are two types of nanoparticle systems consisting of lipid cores formed from solid lipids or mixtures with liquid lipids ^[26][29]. Nanoemulsions are used to increase the bioavailability of hydrophobic drugs and drugs with a high first-pass metabolism. The components of the nanoemulsion system include oils, lipids, surfactants, water-soluble cosolvents, and water ^[27][30]. Lipid-based nano systems represent the largest and most investigated nanocarrier category. Typically, these carriers exhibit a lower toxicity profile and a more reasonable cost compared to polymer carriers ^[28][31]. Among all approaches, the delivery of liposomes and phytosomes is considered to be very effective ^[29][32]. With high biocompatibility and biodegradability, liposomes offer the ability to improve the solubility, efficacy, and bioavailability of drugs. Liposomes can be used to encapsulate hydrophilic and lipophilic drugs ^[30][31][33,34]. Curcumin and tetrandrine are phytochemical compounds that have poor solubility; therefore, their bioavailability is low ^[32][33][35,36]. To overcome this problem, Song, et al. (2022) encapsulated curcumin and tetrandrine in a liposome carrier system ^[34][37]. The results showed high solubility and bioavailability for curcumin and tetrandrine after their encapsulation within the liposome carriers. In addition, in vivo studies have shown no significant toxicity of this system to Zebrafish ^[34][37]. However, liposomes have stability issues and experience self-leakage with particular drugs. Therefore, to protect the stability of liposomes, the stabilizer DSPE–MPEG 2000 (DP) has been widely used ^[28][31]. The addition of DP not only significantly increases the particle size distribution but also significantly increases the encapsulation efficiency and loading dose of curcumin and tetrandrine ^[35][38]. Lipids are considered safe and useful materials for drug delivery. The stability of the system is closely related to the distribution of particle size, lipid content, and surfactant content, which are able to stabilize the dispersion ^[34][37]. Polymers can be used as phytochemical carriers to form structures, such as dendrimers, micelles, polymersomes, etc. The precise classification of polymeric nanocarriers needs further study because, in biomedical and pharmaceutical nanotechnology, no specific limits have been defined. Therefore, there may exist differing perceptions. Examples of natural and synthetic polymers that are often used are alginate, albumin, chitosan, starch, polylactic acid, and Poly(glycolide-co-lactide) (PGLA) ^[36][37][39,40]. Polymers have played an important role in advancing drug delivery technology by providing the controlled release of the active substance in a constant dose over a long period of time ^[38][41]. Polymers protect the drugs via encapsulating, entrapping (inside the core), conjugating, or adsorbing them onto the particle surface ^[39][42] Generally, natural polymers are nontoxic, biocompatible, and biodegradable. Polysaccharides are polymers that are commonly used for the manufacture of polymer-based nanoparticles ^[40][43].