Nanodelivery system of hydroxytyrosol

Hydroxytyrosol is a natural polyphenolic compound with various biological activities. However, its low bioavailability is attributed to poor water solubility and high oxidizability. Nanodelivery systems can effectively address these issues. Below is an overview of targeted designs for liposomes and polymeric micelles as carriers for hydroxytyrosol:

I. Targeted Design of Liposomes

Basic principle: Liposomes are closed bilayer vesicles composed of lipid materials such as phospholipids, exhibiting excellent biocompatibility and biodegradability. Hydroxytyrosol can be encapsulated in the hydrophobic core or embedded in the lipid bilayer of liposomes based on its solubility.

Passive targeting: Leveraging the "enhanced permeability and retention (EPR) effect"—a characteristic of blood vessels in diseased tissues (e.g., tumors) with high permeability and low lymphatic drainage. As nanoscale carriers, liposomes can pass through these leaky blood vessels and passively accumulate in diseased tissues, achieving targeted delivery to pathological sites.

Active targeting: Achieved by modifying the liposome surface with specific targeting ligands, such as antibodies, peptides, or carbohydrates. For example, conjugating antibodies against tumor cell-specific surface antigens to the liposome surface enables specific recognition and binding to tumor cells, thereby delivering hydroxytyrosol precisely into tumor cells. This enhances therapeutic efficacy while reducing damage to normal tissues.

Stimuli-responsive targeting: Liposomes can be designed to respond to specific stimuli, such as pH, temperature, or enzymes. In normal physiological environments, liposomes remain stable; upon reaching diseased sites, the unique microenvironment (e.g., lower pH in tumor tissues or presence of specific enzymes) triggers structural changes in liposomes, leading to rapid release of hydroxytyrosol and achieving targeted delivery with controlled release.

II. Targeted Design of Polymeric Micelles

Basic principle: Polymeric micelles are nanoscale particles self-assembled by amphiphilic polymers in aqueous solutions. Their hydrophobic core can encapsulate hydroxytyrosol, while the hydrophilic shell improves the micelles’ stability and dispersibility in water.

Passive targeting: Similar to liposomes, the nanoscale size of polymeric micelles allows them to utilize the EPR effect, passively accumulating in diseased tissues with vascular leakage, thus realizing targeted delivery of hydroxytyrosol.

Active targeting: Active targeting is also achieved by modifying the micelle surface with targeting ligands. For instance, folate conjugation to polymeric micelles enables targeted delivery to tumor cells, as many tumor cells overexpress folate receptors. Additionally, cell-penetrating peptides can be used as ligands to facilitate micelle penetration through cell membranes, enhancing intracellular uptake of hydroxytyrosol.

Smart targeting: Environment-responsive polymeric micelles enable intelligent targeted delivery. For example, temperature-responsive polymers maintain micelle stability at body temperature but trigger structural changes and hydroxytyrosol release when exposed to locally heated diseased tissues. Alternatively, pH-responsive micelles destabilize in the acidic environment of tumor tissues, rapidly releasing the drug to achieve targeted therapy.

Both liposomes and polymeric micelles, as nanodelivery systems for hydroxytyrosol, effectively improve its targeting, stability, and bioavailability through various targeted design strategies. This broadens the application prospects of hydroxytyrosol in disease treatment, health supplements, and other fields.