Abstract
Two high resolution, 3D imaging techniques were applied to visualize and characterize sterilizing grade dual-layer filtration of liposomes, enabling membrane structure to be related with function and performance. Two polyethersulfone membranes with nominal retention ratings of 650 nm and 200 nm were used to filter liposomes of an average diameter of 143 nm and a polydispersity index of 0.1. Operating conditions including differential pressure were evaluated. X-ray computed tomography at a pixel size of 63 nm was capable of resolving the internal geometry of each membrane. The respective asymmetry and symmetry of the upstream and downstream membranes could be measured, with pore network modeling used to identify pore sizes as a function of distance through the imaged volume. Reconstructed 3D digital datasets were the basis of tortuous flow simulation through each porous structure. Confocal microscopy visualized liposome retention within each membrane using fluorescent dyes, with bacterial challenges also performed. It was found that increasing pressure drop from 0.07 MPa to 0.21 MPa resulted in differing fluorescent retention profiles in the upstream membrane. These results highlighted the capability for complementary imaging approaches to deepen understanding of liposome sterilizing grade filtration.
Highlights
Liposomes consist of a lipid sphere that can carry a payload either within the bilayer or the internal cavity [1,2,3] which is being increasingly explored for advanced therapies [4,5,6]
Liposomes present several challenges at the sterile filtration stage when compared to conventional biologics such as monoclonal antibodies [21,22,23], with one of the most significant being that liposomes are much larger and closer in size to the nominal retention rating (NRR) of a sterile membrane [24,25,26,27]
Liposomes and lipid enveloped products are becoming increasingly prevalent for drug delivery and vaccines, highlighting the need for efficient manufacturing at a scale that requires effective sterilizing grade filtration
Summary
Liposomes consist of a lipid sphere that can carry a payload either within the bilayer or the internal cavity [1,2,3] which is being increasingly explored for advanced therapies [4,5,6]. Liposomes present several challenges at the sterile filtration stage when compared to conventional biologics such as monoclonal antibodies [21,22,23], with one of the most significant being that liposomes are much larger and closer in size to the nominal retention rating (NRR) of a sterile membrane [24,25,26,27] This larger size may result in increased risk of product loss, membrane fouling and bacterial penetration that would impact processing efficiency through blocking mechanisms that are not prevalent when filtering antibodies [28,29]
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