Development and optimization of an automatic liposomes manufacturing method using microfluidics
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Date
2021-06-22
Authors
Rebollo González, René
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Abstract
Despite all their potential and increasing attention in research, lipid nanoparticles, such as liposomes, still present important challenges for their transition into the clinic. Major obstacles to this are the traditional complex methods for manufacture, and the difficulty to scale up and control the process properly.
In this regard, microfluidic-based preparation methods are becoming widely explored for the development of new nanomedicine products, due to their versatility, robustness, and reliability.
In this study, the formulation of PEGylated liposomes and the definition of optimal process conditions in a microfluidic system were accomplished, applying design of experiments (DoE) principles and computational modeling tools.
First, experiments were performed to identify the main factors affecting liposomes characteristics, and to define the optimal conditions for their controlled and robust manufacture. Lipid composition and the process parameters total flow rate (TFR) and flow rate ratio (FRR) were found to be the most influential for the formation of vesicles with an average size under 100 nm and PDI lower than 0.2. Subsequently, data collected was used to build an artificial neural network (ANN) to predict liposome size and size distribution, depending on the formulation and process conditions employed.
The application of automatic manufacturing processes, DoE, and Artificial Intelligence allowed the production and analysis of highly valuable and reliable data with fewer resources and time. The spread of an experimental approach based on the synergy of these tools would allow more efficient development and optimization of other nano-based medications.
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Keywords
Microfluids, Liposomes