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Serum-Stable, Long-Circulating, pH-Sensitive PEGylated Liposomes.

Nicolas Bertrand1, Pierre Simard2, Jean-Christophe Leroux3

  • 1Faculty of Pharmacy, Université Laval, CHU de Quebec Research Center, 2705 Boul Laurier, G1V 1B3, Quebec, QC, Canada.

Methods in Molecular Biology (Clifton, N.J.)
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Summary

pH-sensitive liposomes offer targeted drug delivery to acidic organelles. These novel vesicles release their payload in response to pH changes, enhancing therapeutic efficacy.

Keywords:
N-Isopropylacrylamide copolymerTriggered releasepH-sensitive liposomes

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Area of Science:

  • Biochemistry
  • Materials Science
  • Drug Delivery Systems

Background:

  • Liposomes are widely used for drug delivery, but controlling drug release remains a challenge.
  • Targeting acidic intracellular organelles requires specialized delivery systems.
  • Existing formulations may expose drugs to degradation in lysosomes before reaching the target site.

Purpose of the Study:

  • To design and characterize pH-sensitive liposomes for targeted drug delivery.
  • To achieve controlled drug release in acidic intracellular compartments.
  • To enhance cytoplasmic drug concentrations and therapeutic outcomes.

Main Methods:

  • Synthesis of a hydrophobically modified N-isopropylacrylamide/methacrylic acid copolymer (poly(NIPAM-co-MAA)).
  • Incorporation of the copolymer into the lipid bilayer of sterically stabilized liposomes.
  • Preparation and characterization of large unilamellar pH-sensitive vesicles.

Main Results:

  • Developed serum-stable liposomal formulations with minimal leakage at physiological pH.
  • Demonstrated rapid drug release from liposomes at acidic pH (5.0-5.5).
  • Successfully created pH-sensitive vesicles capable of targeted intracellular drug release.

Conclusions:

  • pH-sensitive liposomes incorporating poly(NIPAM-co-MAA) provide a promising platform for targeted drug delivery.
  • These systems enable environment-controlled drug release, protecting the payload until it reaches acidic organelles.
  • The developed vesicles offer enhanced drug delivery efficiency to intracellular targets.