# Targeted Delivery Strategies for Hydrophilic Phytochemicals
## 3 Hydrophilic Phytochemicalemicals
### Chlorogenic Acid
#### 3.7.3 Carrier-Based Delivery Strategies  
Recent advancements in nanotechnology have significantly improved the bioavailability and transdermal delivery of chlorogenic acid through encapsulation in various carrier systems, including ethosomes, liposomes, nanophytovesicles (NPVs), and chlorogenic acid-hydrogenated soy phosphatidylcholine complex (CA-HSPC) [148; 150; 157] Ethosomes, which are lipid-based vesicles enriched with high concentrations of ethanol, effectively enhance the permeability of chlorogenic acid through the stratum comeum (SC). Ethanol increases the fluidity of the lipid bilayer, disrupting the barrier properties of the SC and allowing CGA to penetrate deeper into the epidermis. In vitro studies have demonstrated that ethosomal formulations not only improve the deposition of chlorogenic acid in the skin but also boost its antioxidant and therapeutic efficacy, especially in cosmetic and dermatological applications [148]. In addition to ethosomes, chlorogenic acid is also efficiently delivered through liposomes, which facilitate its solubility and transport across the lipid layers of the skin. Lipsosomal encapsulation enhances CGA's penetration through the stratum corneum by mimicking the phospholipid arrangement of cellular membranes, leading to deeper tissue absorption [148; 150]. A particularly innovative system for CGA delivery is nanophytovesicles (NPVs), which are specialized phospholipid-based carriers designed to enhance lipid solubility and skin permeability. NPVs containing Phospholipon(r) 90H and LIPOID(r) 5100 create microscopic channels within the SC, significantly increasing CGA's permeation through the lipid matrix. Phospholipon 90H is specifically effective in enhancing stratum corneum penetration, while LIPOID(r) 5100 facilitates deeper interactions with cellular membranes, allowing for improved bioavailability [146]. Additionally, NPVs boost lipid solubility more than 25-fold compared to the pure form of CGA, enhancing its stability and therapeutic impact. This carrier system also bypasses the hepatic first-pass effect, ensuring greater systemic availability of chlorogenic acid after transdermal application [157]. CGA encapsulated in Phospholipid Complex (CA-HSPC) has demonstrated increased stability, protection against oxidative degradation, and enhanced penetration through the stratum corneum. The HSPC (hydrogenated soy phosphatidylcholine) layer acts as a protective barrier, prolonging the release of chlorogenic acid while simultaneously improving its therapeutic effects. This controlled-release mechanism not only reduces the frequency of application but also provides sustained antioxidant protection, particularly against UVA-induced photoaging [148]. The use of these carrier systems--ethosomes, liposomes, nanophytovesicles, and phospholipid complexes--substantially improves the skin penetration, stability, and bioavailability of chlorogenic acid. By optimizing its delivery, these technologies enhance CGA's potential for antioxidant, anti-inflammatory, and anti-aging effects in dermatological and cosmetic formulations.  
Ferulic, caffe, and chlorogenic acids, once ingested and absorbed, primarily circulate as conjugated metabolites--glucuronides and sulfates. These forms not only facilitate excretion but may also exert regulatory and protective functions depending on their biological activity and site of action [108; 109; 145].  
The practical implications of these physicochemical characteristics and delivery mechanisms are further explored in the following section, which provides a comparative overview of their dermal and therapeutic applications.