# Targeted Delivery Strategies for Hydrophilic Phytochemicals
## 3 Hydrophilic Phytochemicalemicals  
Hydrophilic phytochemicals are characterized by a high content of hydroxyl (-OH) and carboxyl (-COOH) groups, which increases their water solubility but simultaneously hinders their permeability across cell membranes and limits bioavailability [90, 91, 92, 93]. Their molecular weight (500-4000 Da), polycyclic structures, and abundance of hydrogen bond donors further reduce passive diffusion and contribute to rapid excretion and metabolic degradation. [PERSON] et al. [94] highlighted that additional limitations in bioavailability result from their instability under environmental conditions--exposure to light, oxygen, pH changes, and elevated temperature can lead to photodegradation, hydrolysis, and oxidation [94]. Recent studies have shown that some phenolic substances (e.g., epicatechin, chlorogenic acid, isoquercetin) are only stable at low temperatures and degrade rapidly at 40 \({}^{\circ}\)C [92, 94, 95]. The excess of hydrogen bond donor groups (-OH and -NH\({}_{2}\)) further impairs passive membrane diffusion, and their complex molecular structures (e.g., polycyclic features) promote swift elimination and metabolic breakdown [94]. They are also subjected to enzymatic degradation and interactions with microbiota and pH, necessitating the development of protective delivery systems [94, 96]. In response, various strategies like advanced skin delivery systems are commonly applied [97]. Hydrophilic particles can undergo destabilization already at the stage of their extraction from plants raw materials. For instance, [PERSON] et al. [98] emphasized the importance of polyphenol solubility, which depends on the number of hydroxyl groups, substituents, and degree of conjugation. The choice of solvents (ethanol, methanol, water) is crucial--high-polarity solvents improve extraction efficiency but may also cause degradation of thermolabile constituents [98, 99]. As alternatives, hydrotropic solvents (e.g., sodium cumenesulfonate (NaCS), sodium \(n\)-butyl benzene sulfonate (NaNBBS)) offer high extraction efficiency, are eco-friendly, non-toxic, and reusable [100]. The application of auxiliary extraction techniques such as MAE (microwave-assisted extraction), UAE (ultrasound-assisted extraction), or EAE (enzyme-assisted extraction) increases extraction efficiency while limiting degradation of active compounds [98, 99, 101]. High hydrostatic pressure (HHPE) and pulsed electric field (PEF) improve cell membrane permeability, allowing cytoplasmic release without damaging compound structures [98]. Due to low membrane permeability (low value of log\(P\)) [102] and high polarity, efficient delivery of hydrophilic compounds requires the use of transport systems. The appropriate selection of surfactants, particle size, and viscosity enhances solubility in lipid environments and boosts bioavailability [103]. Hansen Solubility Parameters (HSP) are used to predict the compatibility of compounds (e.g., phenolic acids and flavonoids) with ionic liquids, emphasizing the need for supportive systems for their isolation and formulation [104]. A great advantage of hydrophilic phytochemicals is their strong biological activity. Their antioxidant and anti-inflammatory properties determine their ability to neutralize free radicals, chelate heavy metals, and modulate pro-inflammatory enzyme expression [91, 105, 106, 107, 103]. A correlation between phenolic content and antioxidant potential of the extracts has been confirmed [108, 109]. Interestingly, thermal processing may even enhance the bioactivity of certain compounds [107]. [PERSON] et al. [94] stated that, the abundance of hydrogen bond donor groups, typical for hydrophilic compounds, limits membrane permeability but supports receptor binding and neutralization of reactive oxygen species (ROS) [94]. Hydrophilic compounds represent a large and diverse group of plant metabolites. These substances are widely distributed in natural raw materials and play important roles in various biological processes.