Abstract

Liposomes are lipid based bilayer vesicles that can encapsulate, deliver and release low-soluble drugs and small molecules to a specific target site in the body. They are currently exploited in several nanomedicine formulations. However, their development and application is still limited by expensive and time-consuming process development and production methods. Therefore, to exploit these systems more effectively and support the rapid translation of new liposomal nanomedicines from bench to bedside, new cost-effective and scalable production methods are needed. We present a continuous process flow system for the preparation, modification and purification of liposomes which offers lab-on-chip scale production. The system was evaluated for a range of small vesicles (below 300 nm) varying in lipid composition, size and charge; it offers effective and rapid nanomedicine purification with high lipid recovery (> 98%) combined with effective removal of non-entrapped drug (propofol >95% reduction of non-entrapped drug present) or protein (ovalbumin >90% reduction of OVA present) and organic solvent (ethanol >95% reduction) in less than 4 minutes. The key advantages of using this bench-top, rapid, process development tool are the flexible operating conditions, interchangeable membranes and scalable high-throughput yields, thereby offering simultaneous manufacturing and purification of nanoparticles with tailored surface attributes.

Highlights

  • Liposomes are lipid based bilayer vesicles that can encapsulate, deliver and release low-soluble drugs and small molecules to a specific target site in the body

  • We successfully investigated the region of operation for the Tangential Flow Filtration (TFF) device with various liposome formulations and confirmed the upper limit of operational pressure for the presented purification system to be 75 psi

  • The membrane remained intact throughout, and it can be considered that the measured backpressure equaled the transmembrane pressure inside the tangential flow filtration (TFF)

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Summary

Introduction

Liposomes are lipid based bilayer vesicles that can encapsulate, deliver and release low-soluble drugs and small molecules to a specific target site in the body They are currently exploited in several nanomedicine formulations. Liposomes are a well-established formulation strategy to improve drug delivery and enhance therapeutic outcomes for a range of drugs, such as pharmaceuticals, biopharmaceuticals, and vaccines Due to their bilayer vesicle structure, which is akin to natural cells, liposomes are able to incorporate drugs both within their aqueous core and their lipidic bilayers. To produce liposomes in a controlled size range, downsizing through extrusion or homogenisation is often adopted This adds further steps to the manufacturing process and exposes the liposomes and drug constituents to harsh www.nature.com/scientificreports/.

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