## 4 Limitations of Using Plant Products as Bioherbicides
### Enhancement of Bioactivity Using Nanotechnology
To date, the encapsulation of phloretin for biofebicidal applications has not been explored. Nevertheless, several studies have examined different encapsulation techniques to enhance the solubility, chemical stability, and bioavailability of phloretin for pharmaceutical and medical applications. Phloretin is known for its human health-beneficial properties. Its beneficial effects are primarily linked to its strong antioxidant properties. Additionally, it influences multiple signaling pathways and molecular mechanisms, providing therapeutic advantages for a range of diseases, such as cancer, diabetes, liver and kidney injuries, encephalomyelitis, ulcerative colitis, asthma, arthritis, and cognitive impairments [274]. The authors discussed the pharmacological actions, underlying mechanisms, and molecular targets of phloretin. Moreover, the review provides insights into physicochemical and pharmacokinetic characteristics and approaches to promote the pharmaceutical development of phloretin for its therapeutic applications in the future, as well as scientific efforts to enhance its bioavailability by modifying its physicochemical properties and molecular structure. Phloretin is known to dissolve readily in methanol, ethanol, acetone, dimethyl sulphoxide, and alkaline solutions. However, its low water solubility and low stability make its usage in clinical applications difficult, especially in water-based formulations. To enhance its dissolution, lipid-based delivery systems, such as nanoemulsions (NEs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), offer a promising approach. These systems are advantageous because the lipids used are biocompatible and biodegradable. NLCs, a sophisticated delivery system made from a combination of solid and liquid lipids, forms an imperfect matrix that efficiently incorporates and protects bioactive compounds [275]. NLCs offer several benefits, including high encapsulation efficiency, stability, non-toxicity, suitability for industrial processing, and sustained release. [PERSON] et al. [276] prepared a phloretin-loaded NLC using high-pressure homogenization. Transmission electron microscopy revealed that the NLC had a spherical shape with uniform distribution, an average particle size of 137.40 \(\pm\) 3.27 nm, and a PGL value of 0.237 \(\pm\) 0.005. The encapsulation efficiency was 96.68 \(\pm\) 0.06%. In vitro release studies demonstrated that the phloretin NLC effectively sustained phloretin release compared to the phloretin ethanol solution. Several studies have reported the successful encapsulation of phloretin and/or phloretin using cyclodext. Cyclodext have a wide range of applications in food, pharmaceutical, medical, cosmetic, and environmental applications due to their low cost, safety, biocompatibility, and biodegradability [277]. [PERSON] et al. [278] thoroughly investigated the inclusion complexes of cyclodext with phloretin, while [PERSON] et al. [279] demonstrated that encapsulation with hydroxypropyl-\(\beta\)-cyclodextrinrin enhances water solubility and preserves the antioxidant capacity of entrapped phloretin. The encapsulation of phloretin and phloretin in cyclodext leads to perpendicular conformations of their pharmaceutically active forms, further highlighting the potential of cyclodext as molecular stabilizers and aqueous solubilizers for improving the bioavailability and efficient delivery of bioactive compounds in food [279]. [PERSON] et al. [280] demonstrated the improved water solubility of phloretin after encapsulation with methyl-\(\beta\)-cyclodextrinrin and 2-hydroxy propyl-\(\beta\)-cyclodextrintrim using the freeze-drying method. The reducing power and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical-scavenging activity tests revealed that the antioxidant activity of phloretin improved after the formation of inclusion complexes. [PERSON] et al. (2018) designed polymer-based nanoparticles as effective oral drug delivery systems capable of enhancing both the systemic bioavailability and therapeutic efficacy of phloretin.