DEVELOPMENT OF A MICROFLUIDIC PLATFORM FOR THE PREPARATION OF SOFT-MATTER NANOPARTICLES FOR APPLICATIONS IN DRUG DELIVERY

This thesis presents the development of microfluidic platform for the controlled preparation of cubosomes which are lipid-based liquid crystalline nanoparticles, with potential applications in drug delivery. The platform was engineered using a microfluidic chip fabricated via fused deposition modeling (FDM), designed to induce chaotic advection and enhance passive mixing efficiency. The system enables precise manipulation of fluid flow and formulation parameters, facilitating the bottom-up self-assembly of cubosomes from an organic lipid phase and an aqueous polymer solution. Glyceryl monooleate (GMO) was used as the lipid matrix, and Pluronic F127 served as the stabilizing polymer. A synthetic mannose-based glycolipid, 6-O-decanoyl-D-mannopyranose (MC10), was also incorporated into select formulations at 10 mol% to evaluate the effect of glycolipid functionalization on nanoparticle properties. A systematic optimization study was conducted by varying the total flow rate (TFR), flow rate ratio (FRR), lipid concentration, and polymer concentration. Results showed that lower lipid concentrations and higher TFRs produced smaller, more monodisperse cubosomes, with optimal conditions identified at 30 mg/mL GMO, 10% F127, TFR 20 mL/min, and FRR 1:3. Particle sizes under these conditions were consistently around 150–170 nm with PDI < 0.12. X-ray diffraction analysis confirmed the formation of the Im3m cubic phase in both GMO and GMO/MC10 systems, with the latter exhibiting an increased lattice parameter and water channel radius, indicating internal structural modification without phase transition.The anticancer drug 5-fluorouracil (5-FU) was encapsulated into both GMO and GMO/MC10 cubosomes using the optimized microfluidic protocol. UV–Vis spectroscopy confirmed a consistent encapsulation efficiency of approximately 20%, with a loading capacity of ~10%. All formulations demonstrated good colloidal stability over 30 days at room temperature, maintaining particle size, low polydispersity, and stable zeta potential values. Notably, the GMO/MC10 formulation showed improved dispersion uniformity over time. In vitro cytotoxicity tests using the MDA-MB-231 breast cancer cell line revealed that 5-FU-loaded cubosomes were more effective in reducing cell viability than the free drug, particularly at therapeutically relevant concentrations (25–100 µM). Although the addition of MC10 did not markedly enhance cytotoxicity in this cell line, the glycolipid’s targeting potential may be more relevant in receptor-expressing models. This work establishes a versatile microfluidic strategy for producing structurally tunable cubosomes and demonstrates their potential as nanocarriers for drug delivery applications