Phd in PHARMACEUTICAL SCIENCES

Thesis title: Design and Development of Soy-Phosphatidylcholine-Based Liposomes and Nanoemulsions for Drug Delivery

This doctoral research addresses the longstanding challenge of designing lipid-based delivery systems, such as liposomes and nanoemulsions, aimed at improving the solubility, stability, and biological performance of bioactive compounds with unfavorable physicochemical properties. Particular attention was given to amphiphilic and hydrophobic molecules, which, despite their promising biological potential, often exhibit instability, volatility, or low bioavailability in conventional formulations. The experimental work is organized into two parts and four chapters (3–6), each focusing on specific formulation strategies or technological aspects, with the overarching goal of elucidating how formulation components, preparation methods, and physical modifiers influence the structural, physicochemical, and functional behavior of lipid-based carriers. Part I investigates the incorporation of amphiphilic molecules into the phospholipid bilayer of liposomes to modulate vesicle properties. Hydrophobic or amphiphilic compounds can alter lipid packing and membrane cooperativity, affecting stability, deformability, and drug release. For instance, β-caryophyllene-loaded liposomes exhibited reduced cellular uptake due to bilayer stiffening, which was mitigated through multilamellar systems and optimized drug/lipid ratios. Conversely, amphiphilic molecules, such as palmitoyl-pentapeptide KTTKS, can enhance bilayer fluidity and vesicle deformability, facilitating transdermal delivery and biological activity, as presented in Chapter 3. Part II focuses on phospholipid-based nanoemulsions for essential oils (EOs), natural compounds with broad-spectrum antimicrobial, antifungal, and insecticidal activity. Nanoencapsulation enhances EO stability, solubility, and bioavailability while enabling controlled release. Chapter 4 details the formulation of Lavandula × intermedia EO nanoemulsions using medium-chain triglycerides (MCT) to prevent Ostwald ripening. Chapter 5 evaluates antifungal activity of Origanum vulgare EO and carvacrol, demonstrating that release kinetics and structural integrity are critical for biological efficacy. Chapter 6 integrates rheological design, exploring the effects of viscosity, viscoelasticity, and hydrocolloid modifiers on stability, flow behavior, and EO release, with complementary strategies including Ghassoul clay incorporation and oil fraction modulation. Collectively, these studies provide a comprehensive understanding of how lipid and active compound characteristics, preparation methods, stabilizing additives, and rheological properties govern the structural organization, stability, and functional performance of lipid-based nanocarriers. This research establishes a rational framework for designing versatile liposomal and nanoemulsion systems capable of delivering unstable or poorly soluble bioactives while ensuring controlled release, biocompatibility, and application-specific performance.