Stabilization Of Liposomes Using Hyaluronic Acid-Modified Gold Nanoparticles by Post-Microfluidics Conjugation Approach for Drug Delivery Applications

Lipid-based nanoparticles (LNPs), particularly liposomes, have gained prominence throughout the pharmaceutical sector as a hopeful means for transporting a range of therapeutic agents. Microfluidics is an emerging technology that can be employed as a powerful tool for designing nanoscale liposomes with highly uniform size distributions and acceptable colloidal stability. The current research was undertaken to design a pH-responsive hyaluronic acid-modified gold nanoparticle-stabilized cationic liposome (SPC/DOPE/DOTAP) system (HA-SH/AuNPs@liposomes). This was achieved through a post-microfluidics conjugation technique to encapsulate the 5-fluorouracil (5-FU) anticancer drug, usually employed in nonmelanoma skin cancer (NMSC) treatment. Utilizing a microfluidics toroidal mixer, affixed HA-SH/AuNPs (size: 12.56 ± 1.65 nm) to positively charged liposomes (size: 75 ± 0.68 nm and PDI: 0.032 ± 0.0021). These liposomes exhibited strong stability, limited fusion propensity, and minimal cargo release at neutral pH. The gold stabilizers detached in an acidic environment (pH < 5), releasing encapsulated therapeutic agents. The dynamic light scattering (DLS) analysis results indicate that HA-SH/AuNPs@Liposomes (size: 102.2 ± 1.3 nm and PDI: 0.11 ± 0.01) exhibit greater stability than bare liposomes over 4 weeks at 4 °C. This enhanced stability can be attributed to the presence of HA-SH/AuNPs in the liposomal structure. This research outlines a systematic method to rapidly optimize the size and PDI of liposomes by employing the Design of Experiments (DoE). The results highlighted that utilizing both the microfluidic technique and gold nanoparticle-stabilized liposomes offers benefits for creating controlled drug release formulations. This approach leads to enhanced biopharmaceutical characteristics and improved scalability of liposomal formulations.