Design of lipid-polymer hybrid nanoparticles using fluidic nanoprecipitation for antibacterial application : formulation optimization using design of experiment approach

• Main Author: Tjiptadi, Jerome Adriel
• Other Authors: Loo Say Chye Joachim
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2021
• Subjects: Engineering::Nanotechnology; Engineering::Materials
• Online Access: https://hdl.handle.net/10356/151133
• Institution: Nanyang Technological University

The purpose of this study was to design lipid-polymer hybrid nanoparticles (LPHNPs) utilizing the design of experiment (DoE) approach for antibacterial application. Nanoformulations were fabricated using one-step fluidic nanoprecipitation method. The primary core material of the LPHNPs was PLGA, whereas DOTAP and DSPC were used as lipid shell layer. The 2^5 full factorial design was implemented to comprehend the significance of each experimental factors on the particle size, polydispersity index, and zeta potential of the LPHNPs. In this study, we evaluated total flow rate (TFR), flow rate ratio (FRR), lipid ratio, polymer concentration, and use of microfluidic chip. The LPHNPs were characterized by dynamic light scattering and field-emission scanning electron microscopy. The optimum formulation of LPHNPs was obtained with FRR (aqueous:organic) of 4:1, lipid ratio (DOTAP:DSPC) of 4:1, PLGA concentration of 10 mg/ml and without the use of microfluidic chip. FRR, PLGA concentration and use of microfluidic chip had profound effect on the mean particle size of LPHNPs, while FRR, lipid ratio, and use of microfluidic chip as well as their interaction with each other had significant effect on the surface charge of LPHNPs. On the contrary, none of the experimental factors were significant to the polydispersity of LPHNPs fabricated. Therefore, the size and zeta potential of LPHNPs formulated by fluidic nanoprecipitation system could be easily adjusted through changes of the aforementioned factors in order to carry antimicrobials for the treatment of biofilm-mediated infections effectively. Overall, the findings of this work are promising to facilitate the screening of different LPHNP-based antimicrobial delivery system during preclinical development.