Abstract
pH-sensitive liposomes have been designed to deliver active compounds, specifically to acidic intracellular organelles and to augment their cytoplasmic concentrations. These systems combine the protective effects of other liposomal formulations with specific environment-controlled drug release. They are stable at physiological pH, but abruptly discharge their contents when endocytosed into acidic compartments, allowing the drug to be released before it is exposed to the harsh environment of lysosomes.
Serum-stable formulations with minimal leakage at physiological pH and rapid drug release at pH 5.0–5.5 can be easily prepared by inserting a hydrophobically modified N-isopropylacrylamide/methacrylic acid copolymer (poly(NIPAM-co-MAA)) in the lipid bilayer of sterically stabilized liposomes. The present chapter describes polymer synthesis, as well as the preparation, and characterization of large unilamelar pH-sensitive vesicles.
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References
Mukherjee S, Ghosh RN, Maxfield FR (1997) Endocytosis. Physiol Rev 77:759–803
Chen G, Hoffman AS (1995) Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature 373:49–52
Meyer O, Papahadjopoulos D, Leroux J-C (1998) Copolymers of N-isopropylacrylamide can trigger pH sensitivity to stable liposomes. FEBS Lett 421:61–64
Leroux J-C (2004) pH-responsive carriers for enhancing the cytoplasmic delivery of macromolecular drugs. Adv Drug Deliv Rev 56:925–926
Leroux J-C, Roux E, Le Garrec D, Hong K, zcopolymers for the preparation of pH-sensitive liposomes and polymeric micelles. J Control Release 72:71–84
Roux E, Francis M, Winnik FM, Leroux J-C (2002) Polymer based pH-sensitive carriers as a means to improve the cytoplasmic delivery of drugs. Int J Pharm 242:25–36
Roux E, Passirani C, Scheffold S, Benoit J-P, Leroux J-C (2004) Serum-stable and long-circulating, PEGylated pH-sensitive liposomes. J Control Release 94:447–451
Roux E, Stomp R, Giasson S, Pézolet M, Moreau P, Leroux J-C (2002) Steric stabilization of liposomes by pH-responsive N-isopropylacrylamide copolymer. J Pharm Sci 91:1795–1802
Zignani M, Drummond DC, Meyer O, Hong K, Leroux J-C (2000) In vitro characterization of a novel polymeric-based pH-sensitive liposome system. Biochim Biophys Acta 1463:383–394
Kitano H, Akatsuka Y, Ise N (1991) pH-responsive liposomes which contain amphiphiles prepared by using lipophilic radical initiator. Macromolecules 24:42–46
Winnik FM, Davidson AR, Hamer GK, Kitano H (1992) Amphiphilic poly(N-isopropylacrylamide) prepared by using a lipophilic radical initiator: Synthesis and solution properties in water. Macromolecules 25:1876–1880
Bartlett GR (1959) Phosphorous assay in column chromatography. J Biol Chem 234:466–468
Satish PR, Surolia A (2002) Preparation and characterization of glycolipid-bearing multilamellar and unilamellar liposomes. In: Basu SC, Basu M (eds) Liposomes: methods and protocols, vol 199. Humana Press, Totowa, NJ, pp 193–202
Zuidam NJ, de Vrueh R, Crommelin DJ (2003) Chapter 2: Characterization of liposomes. In: Torchilin VP, Weissig V (eds) Liposomes: a practical approach. Oxford University Press, Oxford, pp 31–78
Bertrand N, Fleischer JG, Wasan KM, Leroux J-C (2009) Pharmacokinetics and biodistribution of N-isopropylacrylamide copolymers for the design of pH-sensitive liposomes. Biomaterials 30(13):2598–2605. doi:10.1016/j.biomaterials.2008.12.082
Stolnik S, Ilum L, Davis SS (1995) Long circulating microparticulate drug carriers. Adv Drug Deliv Rev 16:194–214
Acknowledgements
Financial support from the CIHR and the FRSQ (scholarships to NB and PS) is acknowledged.
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Bertrand, N., Simard, P., Leroux, JC. (2010). Serum-Stable, Long-Circulating, pH-Sensitive PEGylated Liposomes. In: Weissig, V. (eds) Liposomes. Methods in Molecular Biology, vol 605. Humana Press. https://doi.org/10.1007/978-1-60327-360-2_36
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DOI: https://doi.org/10.1007/978-1-60327-360-2_36
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