US 12,377,048 B2
Methods of making neutral liposomes containing biologically active agents
Richard K. Fisher, Knoxville, TN (US); Deidra J. H. Mountain, Knoxville, TN (US); and Oscar H. Grandas, Knoxville, TN (US)
Assigned to UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION, Knoxville, TN (US)
Filed by UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION, Knoxville, TN (US)
Filed on Jan. 19, 2021, as Appl. No. 17/152,342.
Application 17/152,342 is a continuation of application No. PCT/US2019/042600, filed on Jul. 19, 2019.
Claims priority of provisional application 62/701,759, filed on Jul. 21, 2018.
Prior Publication US 2021/0244665 A1, Aug. 12, 2021
Int. Cl. A61K 9/1273 (2025.01); A61K 9/1277 (2025.01); A61P 9/00 (2006.01); C12N 15/113 (2010.01)
CPC A61K 9/1273 (2013.01) [A61K 9/1277 (2013.01); A61P 9/00 (2018.01); C12N 15/113 (2013.01); C12N 2310/14 (2013.01)] 14 Claims
 
1. A process for preparing liposomes, comprising:
adding a hydrophobic solution to an aqueous composition,
wherein the hydrophobic solution comprises ethanol, neutral lipid bilayer precursors, and a stearylated first nucleic acid condenser, wherein the stearylated first nucleic acid condenser comprises octaarginine (R8) of SEQ ID NO: 6 or SEQ ID NO: 7; and
wherein the aqueous composition comprises a nucleic acid;
wherein liposomes form that have the stearylated first nucleic acid condenser incorporated in a membrane of the liposome and wherein the nucleic acid is encapsulated therein as an aqueous core composition; and
isolating the liposomes, wherein the liposomes are less than 100 nm in diameter with a polydispersity index <0.2.