DEVELOPMENT OF A GREEN TECHNOLOGY-BASED NUTRACEUTICAL FORMULATION USING SUPERCRITICAL CO2. MICROFLUIDIC-ASSISTED FORMULATION AND CHARACTERIZATION OF QUERCETIN LIPOSOMES AND VS10 LIPOSOMES.

The thesis is divided into three chapters, where the Chapter 1 - Development of a Green Technology-Based Nutraceutical Formulation using Supercritical CO2 focuses on developing nanocrystals as a delivery system to preserve the bioavailability of bioactive components and thereby enhancing the parameters such as solubility, permeability, and stability. Supercritical carbon dioxide (Sc-CO2) technology offers a green, sustainable method for both extracting bioactive substances and producing delivery systems. Quercetin as a bioactive component was chosen based on its multifaceted functions but because of its hydrophobicity, low bioavailability nanocrystals an encapsulated system were prepared. Quercetin nanocrystals, produced using the Solvent Antisolvent (SAS) method, was encapsulated using Pluronic F127 and 2-Hydroxypropyl β-cyclodextrin (2-HP-β-CD) improved solubility and stability, as confirmed by FTIR, DSC, XRD analysis. Thermal and kinetic studies demonstrated stability up to 100°C and sustained drug release in intestinal and gastric media. Quercetin nanocrystals were prepared using the Supercritical CO2 and Liquid CO2, as an antisolvent. The nanocrystals prepared using the CO2 based mechanism were compared with the batch method of preparation namely Solvent injection method. The results obtained showed comparatively better solubility, stability, molecular interactions and release profile of the nanocrystals prepared using the CO2 based technology. Further, Chapter 2 - Microfluidic-Assisted Formulation and Characterization of Quercetin- Loaded Liposomes for Enhanced Oral Delivery was the PhD project performed in collaboration with Galenica Senese. The aim was to obtained an optimized liposomal delivery system as an antioxidant supplement of quercetin using food-grade, FDA-approved excipients. The liposomal preparation was achieved using the microfluidics technology. These formulations demonstrated consistent particle sizes (100–150 nm), low polydispersity index (PDI < 0.3), and high stability, as validated by TEM analysis. Safety studies confirmed no cytotoxic effects on healthy cells at concentrations above 100 μM. In Chapter 3 - Microfluidic-Based Development of VS10-Loaded Liposomes as a Chemotherapeutic for Targeted Pin1 Inhibition involved the microfluidics technology that enabled the development of VS10 liposome. VS10 is a PIN1 inhibitor which interacts with the critical active sites and mediate the degradation of Pin 1 but VS10 is a BCS class 2 drug and thus provide low solubility and bioavailability. Hence it was encapsulated in liposomes that achieved 80% efficiency, significantly reducing IC50 values in ovarian cancer cell lines. This multidisciplinary approach highlights the potential of green technologies and advanced delivery systems in maximizing the therapeutic and preventive benefits of bioactive compounds.