title: Characterization of drug encapsulation and retention in archaea-inspired tetraether liposomes.
abstract: The passive leakage of small molecules across membranes is a major limitation of liposomal drug formulations. Here, we evaluate the leakage of 3 clinically used chemotherapeutic agents (cytarabine, methotrexate and vincristine) encapsulated in liposomes comprised of a synthetic, archaea-inspired, membrane-spanning tetraether lipid. Liposomes comprised of the pure tetraether lipid exhibited superior retention of both a neutrally and positively charged drug (up to an ∼9-fold decrease in the rate of drug leakage) compared to liposomes formed from a commercial diacyl lipid, while exhibiting a similar retention of a negatively charged drug that did not appreciably leak from either type of liposome. We also demonstrate that liposomes made of the archaea-inspired lipid can be used for the delivery of encapsulated small molecules into living cells.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA. jerryyang@ucsd.edu.
authors.forename: Geoffray
authors.initials: G
authors.lastname: Leriche
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA. jerryyang@ucsd.edu.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Cifelli
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA. jerryyang@ucsd.edu.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Sibucao
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA. jerryyang@ucsd.edu.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Patterson
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA. jerryyang@ucsd.edu.
authors.forename: Takaoki
authors.initials: T
authors.lastname: Koyanagi
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA. jerryyang@ucsd.edu.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Gianneschi
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA. jerryyang@ucsd.edu.
authors.forename: Jerry
authors.identifier: http://orcid.org/0000-0002-8423-7376
authors.initials: J
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis* / Q000737:chemistry*; D001105:Archaea / Q000737:chemistry*; D004339:Drug Compounding; D006801:Humans; D007624:KB Cells; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D008081:Liposomes