## 4 Limitations of Using Plant Products as Bioherbicides
### Enhancement of Bioactivity Using Nanotechnology
Phloretin-loaded polymeric nanocomposites were prepared using ionic gelation and optimized for yield, encapsulation, loading, particle size, PdI, and zeta potential. Results indicated enhanced oral bioavailability and antioxidant capacity, as well as reduced myocardial infarct size in an ischemia-induced rat model by -46% versus -13% for free phloretin, showing significant cardiomyocyte protection and ROS suppression. To facilitate the transdermal administration of phloretin, polymeric microspheres based on gallic acid were obtained by a reverse-phase emulsion radical polymerization reaction and characterized by transformed infrared spectroscopy ([PERSON] et al., 2018). The tests revealed that particle swelling increases over time, enhancing the release of phloretin from the matrix. Preliminary studies investigating the release behavior of phloretin demonstrated that the particles efficiently release phloretin upon contact with the skin, showing performance comparable to that of a free drug solution. Furthermore, the microspheres successfully protected phloretin from degradation, as confirmed by mass spectrometry analysis. Antioxidant activity testing in rat liver microsomes revealed time-dependent effects, with higher activity observed in microspheres loaded with phloretin compared to unloaded ones. Collectively, these findings suggest that gallic acid-based microspheres have potential as transdermal carriers for phloretin, offering protection and therapeutic benefits against UV radiation-induced skin damage. [PERSON] et al. (2018) reported potent antioxidant and anti-carcinogenic effects of phloretin-loaded chitosan nanoparticles in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral cancer in experimental animals. Over the past two decades, chitosan-formulated nanoparticles have been extensively investigated for their efficiency in delivering chemotherapeutic drugs to target cancer cells. Numerous studies have highlighted the superior biocompatibility and biodegradability of phytochemical-encapsulated chitosan nanoparticles compared to other nanoparticle formulations. Treatment with phloretin-loaded chitosan nanoparticles significantly reduced tumor volume and neoplastic changes and enhanced mitochondrial-mediated apoptosis in tumor cells. [PERSON] et al. (2018) chemically modified a phytoglycogen structure to introduce negative surface charges via carboxymethylation (CMPG) and then prepared CMPG-based ternary nanocomposite particles. This was achieved via electrostatic interactions with sodium caseinate (forming the core) and chemical cross-linking with pectin (forming the shell). The resulting nanocomposite demonstrated remarkable efficiency in encapsulating phloretin, a model lipophilic bioactive compound. Moreover, it exhibited slow and sustained release of phloretin under simulated gastrointestinal conditions and significantly enhanced its antioxidant activity in an aqueous environment compared to pure phloretin dissolved in ethanol. The collected studies suggest that encapsulating phloretin is an effective strategy for improving its solubility, chemical stability, and bioavailability, making it suitable for pharmaceutical and medical applications. Furthermore, these encapsulation techniques hold great potential for developing phloretin-based bioherbicidal formulations, supporting organic and sustainable agricultural practices.