Preparation of atorvastatin calcium-loaded liposomes using thin-film hydration and coaxial micromixing methods: A comparative study
Faezeh Dangkoub, Mehri Bemani Naeini, Shima Akar, Ali Badiee, Mahmoud Reza Jaafari, Mojtaba Sankian, Mohsen Tafaghodi, Seyed Ali Mousavi Shaegh
Abstract
Development of techniques to produce nanoformulations in a controlled and reproducible manner is of great importance for research, clinical trials, and industrial scale-up. This research aimed to introduce a cost-effective micromixing approach for the nanoassembly of liposomes and compared with thin-film hydration (TFH) method. Numerical simulations and design of experiments (DOE) by response surface methodology (RSM) were used to evaluate the effects of input parameters on liposome properties, aiming to identify optimal conditions. Anionic liposomes without or with atorvastatin calcium (ATC) produced using TFH and the micromixing methods showed similar characteristics in size (150–190 nm), PDI (<0.2), and zeta potential (−50 to −60 mV). Both methods achieved about 70 % encapsulation efficiency with similar drug release profile for ATC-containing liposomes. Analysis of stability and DSC thermograms revealed comparable outcomes for liposomes prepared using both techniques. Nanoliposomes produced via both approaches indicated similar in vitro biological performance regarding cellular uptake and cell viability. The micromixing approach presented an alternative method to produce nanoliposomes in a one-step manner with high controllability and reproducibility without requiring specialized equipment. Compatibility of the micromixer with various solvents, including those detrimental to conventional microfluidic materials like PDMS and thermoplastics, enables exploration of a wide range of formulations. • A metallic-glass micromixer, resistant to various solvents to produce a wide range of formulations was developed. • The cost-effective coaxial micromixer produced liposomal nanocarriers (NCs) in a single step using nanoprecipitation method. • Liposomes made by micromixing method in a continuous manner showed similar results to those produced by TFH approach. • Compared to TFH, the micromixing method provided high controllability and reproducibility, using a few items of equipment.