Hi !

Phospholipid–Drug Complex in Phytosomes In phytosomes, the drug (usually a phytoconstituent) forms stable hydrogen bonds and polar–nonpolar interactions with the phospholipid head group in an organic solvent, creating a stoichiometric molecular complex. This makes the drug an integral part of the lipid structure rather than just being entrapped.

Difference from Liposomes Whereas, liposomes are formed in aqueous media by self-assembly of phospholipid bilayers, physically encapsulating drugs without molecular bonding. Phytosomes, made via solvent-based complexation, yield discrete drug–lipid conjugates without forming large aqueous-core vesicles.

References in support:

Article Phytosomes as Innovative Delivery Systems for Phytochemicals...

Article Liposomes and phytosomes: Nanocarrier systems and their appl...

Article Phytosome and liposome: The beneficial encapsulation systems...

Thank you for your valuable insight, but i want to know how this kind of stoichiometric molecular complex is not formed in case of liposome as same phospholipid and biomolecule can be used in fabricating both phytosome and liposome.

The fundamental distinction between phytosomes and liposomes lies in their preparation methods and resulting molecular architectures, which stem from differences in how the active compounds interact with lipid components. Liposomes are formed through physical encapsulation, where phospholipids self-assemble into concentric bilayer vesicles in aqueous media, creating distinct compartments - an inner aqueous core for hydrophilic drugs and a hydrophobic bilayer region for lipophilic compounds. This process, typically achieved through thin-film hydration followed by sonication or extrusion, relies entirely on the amphiphilic nature of phospholipids and their spontaneous organization in water, without any chemical bonding between the drug and lipid components. In contrast, phytosomes are prepared through a molecular complexation technique where the active phytochemical (typically a plant-derived polyphenol, flavonoid, or terpenoid) forms stoichiometric complexes with phospholipids, primarily phosphatidylcholine, through hydrogen bonding and polar interactions between the polar headgroups of the phospholipids and specific functional groups (such as -OH or -COOH) of the phytochemical. This chemical interaction occurs in aprotic organic solvents like ethanol or acetone before solvent evaporation, resulting in a unique molecular architecture where each phytochemical molecule is tightly associated with phospholipid molecules rather than being physically entrapped.

The preparation methodology critically determines the final structural characteristics: liposomes maintain their classic vesicular morphology with aqueous compartments and bilayer membranes visible by electron microscopy, while phytosomes form non-vesicular, micelle-like structures where the phytochemical becomes an integral part of the lipid matrix. This structural difference has significant implications for stability and bioavailability - phytosomes demonstrate superior membrane affinity and absorption because their phospholipid-phytochemical complexes can more readily integrate with cellular membranes, whereas liposomes rely on passive fusion or endocytosis mechanisms. Additionally, the chemical bonding in phytosomes prevents drug leakage and enhances stability compared to liposomes, where drug retention depends on physical trapping. The choice between these systems depends on the nature of the active compound: liposomes are versatile carriers for both hydrophilic and hydrophobic drugs, while phytosomes are particularly effective for enhancing the delivery of poorly water-soluble plant-derived bioactive compounds with appropriate hydrogen-bonding capacity. Advanced characterization techniques such as FTIR spectroscopy, DSC, and electron microscopy are essential to verify these structural differences, with phytosomes showing evidence of molecular complexation through shifted vibrational frequencies and altered phase transition behavior compared to simple mixtures of components.

Thank you for your valuable insight in this regards