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Materials 2017, 10(12), 1411;

Continuous-Flow Production of Injectable Liposomes via a Microfluidic Approach

CNR NANOTEC-Institute of Nanotechnology, c/o Campus Ecotekne, University of Salento, via Monteroni, 73100 Lecce, Italy
Department of Mathematics and Physics “E. De Giorgi”, University of Salento, via Arnesano, 73100 Lecce, Italy
Janssen Pharmaceutical Company of Johnson & Johnson, via C. Janssen, Borgo S. Michele, 04100 Latina, Italy
Author to whom correspondence should be addressed.
Received: 30 October 2017 / Revised: 24 November 2017 / Accepted: 7 December 2017 / Published: 10 December 2017
(This article belongs to the Special Issue Hard and Soft Hybrid Functional Materials)
PDF [1600 KB, uploaded 10 December 2017]


Injectable liposomes are characterized by a suitable size and unique lipid mixtures, which require time-consuming and nonstraightforward production processes. The complexity of the manufacturing methods may affect liposome solubility, the phase transition temperatures of the membranes, the average particle size, and the associated particle size distribution, with a possible impact on the drug encapsulation and release. By leveraging the precise steady-state control over the mixing of miscible liquids and a highly efficient heat transfer, microfluidic technology has proved to be an effective and direct methodology to produce liposomes. This approach results particularly efficient in reducing the number of the sizing steps, when compared to standard industrial methods. Here, Microfluidic Hydrodynamic Focusing chips were produced and used to form liposomes upon tuning experimental parameters such as lipids concentration and Flow-Rate-Ratios (FRRs). Although modelling evidenced the dependence of the laminar flow on the geometric constraints and the FRR conditions, for the specific formulation investigated in this study, the lipids concentration was identified as the primary factor influencing the size of the liposomes and their polydispersity index. This was attributed to a predominance of the bending elasticity modulus over the vesiculation index in the lipid mixture used. Eventually, liposomes of injectable size were produced using microfluidic one-pot synthesis in continuous flow. View Full-Text
Keywords: liposomes; microfluidics; microreactors liposomes; microfluidics; microreactors

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Zizzari, A.; Bianco, M.; Carbone, L.; Perrone, E.; Amato, F.; Maruccio, G.; Rendina, F.; Arima, V. Continuous-Flow Production of Injectable Liposomes via a Microfluidic Approach. Materials 2017, 10, 1411.

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