On-Chip Fabrication of Paclitaxel-Loaded Chitosan Nanoparticles for Cancer Therapeutics

• Published in: Advanced functional materials Vol. 24; no. 4; pp. 432 - 441
• Main Authors: Majedi, Fatemeh Sadat, Hasani-Sadrabadi, Mohammad Mahdi, VanDersarl, Jules John, Mokarram, Nassir, Hojjati-Emami, Shahirar, Dashtimoghadam, Erfan, Bonakdar, Shahin, Shokrgozar, Mohammad Ali, Bertsch, Arnaud, Renaud, Philippe
• Format: Journal Article
• Language: English
• Published: Blackwell Publishing Ltd 01-01-2014
• Subjects: cancer therapeutics; Chitosan; drug delivery; lab on chip devices; microfluidics; nanoparticles
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201301628

The use of solvent‐free microfluidics to fine‐tune the physical and chemical properties of chitosan nanoparticles for drug delivery is demonstrated. Nanoparticle self‐assembly is driven by pH changes in a water environment, which increases biocompatibility by avoiding organic solvent contamination common with traditional techniques. Controlling the time of mixing (2.5–75 ms) during nanoparticle self‐assembly enables us to adjust nanoparticle size and surface potential in order to maximize cellular uptake, which in turn dramatically increases drug effectiveness. The compact nanostructure of these nanoparticles preserves drug potency better than previous nanoparticles, and is more stable during long‐term circulation at physiological pH. However, when the nanoparticles encounter a tumor cell and the associated drop in pH, the drug contents are released. Moreover, the loading efficiency of hydrophobic drugs into the nanoparticles increases significantly from previous work to over 95%. The microfluidic techniques used here have applications not just for drug‐carrying nanoparticle fabrication, but also for the better control of virtually any self‐assembly process.
Using microfluidics to precisely regulate self‐assembly conditions, a number of nanoparticle properties are tuned to optimize drug‐delivery efficacy. These parameters include size, zeta potential, and pH responsiveness. These nanoparticles are stable during circulation at physiological pH, but if they encounter a tumor cell, where the pH is lower, they rapidly release their anti‐cancer drug cargo