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Characterization of drug encapsulation and retention in archaea-inspired tetraether liposomes.

  • Author(s): Leriche, Geoffray
  • Cifelli, Jessica L
  • Sibucao, Kevin C
  • Patterson, Joseph P
  • Koyanagi, Takaoki
  • Gianneschi, Nathan C
  • Yang, Jerry
  • et al.
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.

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