Serial filtration to generate small cholesterol-containing liposomes
Inventors
Assignees
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Publication Number
US-12350369-B2
Publication Date
2025-07-08
Expiration Date
Abstract
The present invention provides methods and systems for producing liposomes by filtration. The methods include passing a heated lipid suspension through a filter assembly comprising two or more filters connected in series, wherein an orifice is disposed between adjacent filters. The methods and systems can produce liposomes having an average diameter that is less than half the diameter of the filter pores. Further, the methods and systems can produce liposomes with <100 nm average diameter, even when the liposomes comprise at least 30% sterol.
Core Innovation
The invention provides a system for producing liposomes from a lipid suspension using a filter housing with an inlet and an outlet. A filter assembly disposed inside the filter housing includes two or more filters disposed in series, and a panel between adjacent filters includes a central orifice that constricts flow of the lipid suspension through the central orifice.
The orifice has a diameter that is less than an average diameter of the two or more filters. Liposomes produced by passing the lipid suspension through the system at a pressure in the filter assembly less than 300 psi are smaller in diameter and more monodisperse than liposomes produced with the same number of filters not in series.
The disclosure also includes serial filtration of a heated cholesterol/sterol-containing lipid suspension using two or more filters in series with an inter-filter orifice, with reported quantitative comparisons to stacked (non-series) membranes and extrusion methods.
Claims Coverage
The partial claim set includes one independent claim. It covers a filter-based liposome production system with serial filters separated by constricting orifices, where the orifice diameter is smaller than the average filter diameter, and operation at a filter-assembly pressure less than 300 psi yields liposomes that are smaller in diameter and more monodisperse than production using the same number of filters not in series.
Serial filters in a filter housing
A filter housing having an inlet and an outlet, and a filter assembly disposed inside the filter housing, the filter assembly comprising two or more filters disposed in series.
Constricting central orifice between adjacent filters
A panel comprising an orifice disposed between a pair of adjacent filters, wherein an outer surface of the panel surrounding the central orifice is configured to constrict the flow of a lipid suspension between the adjacent filters through the central orifice.
Orifice diameter less than average filter diameter
The orifice has a diameter that is less than an average diameter of the two or more filters.
Pressure less than 300 psi for smaller and more monodisperse liposomes
Liposomes produced by passing the lipid suspension through the system at a pressure in the filter assembly less than 300 psi are smaller in diameter and more monodisperse than liposomes produced with the same number of filters not in series.
The inventive concept is the combination of serial filters within a filter housing and inter-filter constricting orifices whose diameter is less than the average filter diameter, with operation under pressure less than 300 psi to produce liposomes that are smaller in diameter and more monodisperse than liposomes made with the same number of filters not arranged in series.
Stated Advantages
Liposomes produced are smaller in diameter than liposomes produced with the same number of filters not in series.
Liposomes produced are more monodisperse than liposomes produced with the same number of filters not in series.
Reduced required pressurization is reported (typically <300 psi).
Controlled size is reported as a function of the number of filters and passes.
Documented Applications
Producing liposomes from a lipid suspension using a filter housing with an inlet and outlet and a filter assembly having two or more filters disposed in series with constricting inter-filter orifices.
Formulating cholesterol/sterol-containing lipid suspensions and producing liposomes from heated cholesterol/sterol-containing lipid suspensions.
Assessing or reporting comparisons to stacked (non-series/orifice) membranes and extrusion methods for producing liposomes.
Evaluating PEG-lipid effects in the described formulations and related liposome outcomes.
Discussing storage stability in the context of the produced liposomes.
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