Skip to main content
SpringerLink
Log in

Synthesis and characterization of a series of carbamate-linked cationic lipids for gene delivery

  • Articles
  • Published:
Lipids

Abstract

A series of pH-sensitive lipids, 1a-h [(2,3-bis-alkyl-carbamoyloxy-propyl)-trialkylammonium halide] and 2a-d (1-dimethylamino-2,3-bis-alkylcarbamoyloxy-propane), with carbamate linkages between the hydrocarbon chains and an ammonium or tertiary amine head, were synthesized for liposome-mediated gene delivery. The variable length of the carbon chains and the quaternary ammonium or neutral tertiary amine heads allowed us to identify the structure-function relationship showing how these factors would affect cationic lipid in gene delivery performance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

APCI:

atmospheric pressure chemical ionization

API-ES:

atmospheric pressure ionization-electrospray

BTC:

bis(trichloromethyl)carbonate

DODAB:

dioctadecyldimethylammonium bromide

DODAC:

dioctadecyldimethylammonium chloride

HRMS:

high-resolution mass spectrometry

TEM:

transmission electron microscopy

References

  1. Felgner, P.L., Gadek, T.R., Holm, M., Roman, R., Chan, H.W., Wenz, M., Northrop, J.P., Ringold, G.M., and Danielsen, M. (1987) Lipofection: A Highly Efficient, Lipid-Mediated DNA-Transfection Procedure, Proc. Natl. Acad. Sci. USA 84, 7413–7417.

    Article  PubMed  CAS  Google Scholar 

  2. Miller, A.D. (1998) Cationic Liposomes for Gene Therapy, Angew. Chem. Int. Ed. 37, 1768–1785.

    Article  Google Scholar 

  3. Zhang, S.B., Xu, Y.M., Wang, B., Qiao, W.H., Liu, D.L., and Li, Z.S. (2004) Cationic Compounds Used in Lipoplexes and Polyplexes for Gene Delivery, J. Controlled Release 100, 165–180.

    Article  CAS  Google Scholar 

  4. Leventis, R., and Silvius, J.R. (1990) Interactions of Mammalian Cells with Lipid Dispersions Containing Novel Metabolizable Cationic Amphiphiles, Biochim. Biophys. Acta 1023, 124–132.

    Article  PubMed  CAS  Google Scholar 

  5. Bennett, M.J., Malone, R.W., and Nantz, M.H. (1995) A Flexible Approach to Synthetic Lipid Ammonium Salts for Polynucleotide Transfection, Tetrahedron Lett. 36, 2207–2210.

    Article  CAS  Google Scholar 

  6. Kikuchi, I.S., and Carmona-Ribeiro, A.M. (2000) Interactions Between DNA and Synthetic Cationic Liposomes, J. Phys. Chem. B 104, 2829–2835.

    Article  CAS  Google Scholar 

  7. Kim, A., Lee, E.H., Choi, S.H., and Kim, C.K. (2004) In vitro and in vivo Transfection Efficiency of a Novel Ultradeformable Cationic Liposome, Biomaterials 25, 305–313.

    Article  PubMed  CAS  Google Scholar 

  8. Gao, X., and Huang, L. (1991) A Novel Cationic Liposome Reagent for Efficient Transfection of Mammalian Cells, Biochem. Biophys. Res. Commun. 179, 280–285.

    Article  PubMed  CAS  Google Scholar 

  9. Bottega, R., and Epand, R.M. (1992) Inhibition of Protein Kinase C by Cationic Amphiphiles, Biochemistry 31, 9025–9030.

    Article  PubMed  CAS  Google Scholar 

  10. Walker, S., Sofia, M.J., Kakarla, R., Kogan, N.A., Wierichs, L., Longley, C.B., Bruker, K., Axelrod, H.R., Midha, S., Babu, S., and Kahne, D. (1996) Cationic Facial Amphiphiles: A Promising Class of Transfection Agents, Proc. Natl. Acad. Sci. USA 93, 1585–1590.

    Article  PubMed  CAS  Google Scholar 

  11. Smith, A.E. (1995) Viral Vectors in Gene Therapy, Annu. Rev. Microbiol. 4, 807–838.

    Article  Google Scholar 

  12. Smith, L.C., Duguid, J., Wadhwa, M.S., Logan, M.J., Tung, C.H., Edwards, V., and Sparrow, J.T. (1998) Synthetic Peptidebased DNA Complexes for Nonviral Gene Delivery, Adv. Drug Deliv. Rev. 30, 115–131.

    Article  PubMed  CAS  Google Scholar 

  13. Rittner, K., Benavente, A., Bompard-Sorlet, A., Heitz, F., Divita, G., Brasseur, R., and Jacobs, E. (2002) New Basic, Membrane-Destabilizing Peptides for Plasmid-based Gene Delivery in vitro and in vivo, Mol. Ther. 5, 104–114.

    Article  PubMed  CAS  Google Scholar 

  14. El-Aneed, A. (2004) An Overview of Current Delivery Systems in Cancer Gene Therapy, J. Controlled Release 94, 1–14.

    Article  CAS  Google Scholar 

  15. Boussif, O., Lezoualc’h, F., Zanta, M.A., Mergny, M.D., Scherman, D., Demeneix, B., and Behr, J.P. (1995) A Novel, Versatile Vector for Gene and Oligonucleotide Transfer into Cells in Culture and in vivo: Polyethylenimine, Proc. Natl. Acad. Sci. USA 92, 7297–7301.

    Article  PubMed  CAS  Google Scholar 

  16. Lampela, P., Elomaa, M., Ruponen, M., Urtti, A., Männistö, P.T., and Raasmaja, A. (2003) Different Synergistic Roles of Small Polyethylenimine and Dosper in Gene Delivery, J. Controlled Release 88, 173–183.

    Article  CAS  Google Scholar 

  17. Wu, G.Y., and Wu, C.H. (1987) Receptor Mediated in vitro Gene Transformation by a Soluble DNA Carrier System, J. Biol. Chem. 262, 4429–4432.

    PubMed  CAS  Google Scholar 

  18. Ward, C.M., Pechar, M., Oupicky, D., Ulbrich, K., and Seymour, L.W. (2002) Modification of pLL/DNA Complexes with a Multivalent Hydrophilic Polymer Permits Folate-Mediated Targeting in vitro and Prolonged Plasma Circulation in vivo, J. Gene Med. 4, 536–547.

    Article  PubMed  CAS  Google Scholar 

  19. Hood, J.D., Bednarski, M., Frausto, R., Guccione, S., Reisfeld, R.A., Xiang, R., and Cheresh, D.A. (2002) Tumor Regression by Targeted Gene Delivery to the Neovasculature, Science 296, 2404–2407.

    Article  PubMed  CAS  Google Scholar 

  20. Cavazzana-Calvo, M., Thrasher, A., and Mavilio, F. (2004) The Future of Gene Therapy, Nature 427, 779–781.

    Article  PubMed  CAS  Google Scholar 

  21. Liu, D.L., Hu, J.J., Qiao, W.H., Li, Z.S., Zhang, S.B., and Cheng, L.B. (2005) Synthesis of Carbamate-Linked Lipids for Gene Delivery, Bioorg. Med. chem. Lett. 15, 3147–3150.

    Article  PubMed  CAS  Google Scholar 

  22. Kokotos, G., Verger, R., and Chiou, A. (2000) Synthesis of 2-Oxo Amide Triacylglycerol Analogues and Study of Their Inhibition Effect on Pancreatic and Gastric Lipases, Chem. Eur. J. 6, 4211–4217.

    Article  CAS  Google Scholar 

  23. Boomer, J.A., and Thompson, D.H. (1999) Synthesis of Acid-Labile Diplasmenyl Lipids for Drug and Gene Delivery Applications, Chem. Phys. Lipids 99, 145–153.

    Article  PubMed  CAS  Google Scholar 

  24. Boomer, J.A., Thompson, D.H., and Sullivan, S.M. (2002) Formation of Plasmid-based Transfection Complexes with an Acid-Labile Cationic Lipid: Characterization of in vitro and in vivo Gene Transfer, Pharm. Res. 19, 1292–1301.

    Article  PubMed  CAS  Google Scholar 

  25. Bangham, A.D., Standish, M.M., and Watkins, J.C. (1965) Diffusion of Univalent Ions Across the Lamellae of Swollen Phospholipids, J. Mol. Biol. 13, 238–253.

    Article  PubMed  CAS  Google Scholar 

  26. Rider, T.H., and Hill, A.J. (1930) Studies of Glycidol. I. Preparation from Glycerol Monochlorohydrin, J. Am. Chem. Soc. 52, 1521–1527.

    Article  CAS  Google Scholar 

  27. National Institute of Advanced Industrial Science and Technology (AIST), Spectral Database for Organic Compounds, SDBS, http://www.aist.go.jp/RIODB/SDBS/cgi-bin/direct_frame_top.cgi?lang=eng (accessed July, 2005).

  28. Ruth, J.M., and Philippe, R.J. (1966) Mass Spectra of Isocyanates, Anal. Chem. 38, 720–723.

    Article  CAS  Google Scholar 

  29. Alquist, F.N., and Slagh, H.R. (1939) Manufacture of 1-Dimethylamino-2,3-propanediol, U.S. Patent 2,147,226.

  30. Chinese Statistics Society (1985) Orthogonal Test and Thrice Design, pp. 1–100, Science Press, Beijing (in Chinese).

    Google Scholar 

  31. Chen, Y. (1981) Organic Analysis, pp. 713–716, Higher Education Press, Beijing (in Chinese).

    Google Scholar 

  32. Cotarca, L., Delogu, P., Nardelli, A., and Šunjić, V. (1996) Bis(trichloromethyl) Carbonate in Organic Synthesis, Synthesis 5, 553–576.

    Article  Google Scholar 

  33. Wang, X.Z., Li, X.Q., Shao, X.B., Zhao, X., Deng, P., Jiang, X.K., Li, Z.T., and Chen, Y.Q. (2003) Selective Rearrangements of Quadruply Hydrogen-Bonded Dimer Driven by Donor-Acceptor Interaction, Chem. Eur. J. 9, 2904–2913.

    Article  CAS  Google Scholar 

  34. Moniruzzaman, M., Goodbrand, B., and Sundararajan, P.R (2003) Morphology and Thermal Behavior of Self-Assembling Carbamates, J. Phys. Chem. B 107, 8416–8423.

    Article  CAS  Google Scholar 

  35. Feitosa, E., Barreleiro, P.C.A., and Olofsson, G. (2000) Phase Transition in Dioctadecyldimethylammonium Bromide and Chloride Vesicles Prepared by Different Methods, Chem. Phys. Lipids 105, 201–213.

    Article  PubMed  CAS  Google Scholar 

  36. Feitosa, E., and Brown, W. (1997) Fragment and Vesicle Structures in Sonicated Dispersions of Dioctadecyldimethylammonium Bromide, Langmuir 13, 4810–4816.

    Article  CAS  Google Scholar 

  37. Cuccovia, I.M., Sesso, A., Abuin, E.B., Okino, P.F., Tavares, P.G., Campos, J.F.S., Florenzano, F.H., and Chaimovich, H. (1997) Characterization of Dioctadecyldimethylammonium Chloride Vesicles Prepared by Membrane Extrusion and Dichloromethane Injection, J. Mol. Liq. 72, 323–336.

    Article  CAS  Google Scholar 

  38. Uchegbu, I.F., and Vyas, S.P. (1998) Non-ionic Surfactant based Vesicles (niosomes) in Drug Delivery, Int. J. Pharm. 172, 33–70.

    Article  CAS  Google Scholar 

  39. Basu, R., De, S., and Nandy, P. (1998) Effect of n-Decane on Lecithin Phase Transition Temperatures: A Microscopic Study, Colloids Surf. B: Biointerfaces 11, 29–31.

    Article  CAS  Google Scholar 

  40. Hata, T., Matsuki, H., and Kaneshina, S. (2000) Effect of Local Anesthetics on the Phase Transition Temperatures of Ether- and Ester-Linked Phospholipid Bilayer Membranes, Colloids Surf. B: Biointerfaces 18, 41–50.

    Article  CAS  Google Scholar 

  41. Uchegbu, I.F., Schätzlein, A., and Florence, A.T. (1996) Nonionic Surfactant Vesicle (niosome) Phase Transitions, Eur. J. Pharm. Sci. 4 (Suppl. 1), S138.

    Article  Google Scholar 

  42. Uchegbu, I.F., and Florence, A.T. (1995) Non-ionic Surfactant Vesicles (niosomes): Physical and Pharmaceutical Chemistry, Adv. Colloid Interface Sci. 58, 1–55.

    Article  CAS  Google Scholar 

  43. Harris, J.R., Roos, C., Djalali, R., Rheingans, O., Maskos, M., and Schmidt, M. (1999) Micron 30, 289–298.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, Dalian Nationalities University, 116600, Dalian, China

    Shubiao Zhan

  2. State Key Laboratory of Fine Chemicals, Dalian University of Technology, Zhongshan Rd. 158th, 116012, Dalian, China

    Dongliang Liu, ianjun Hu, Weihong Qiao, Zongshi Li & Lvbo Cheng

Authors
  1. Dongliang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. ianjun Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weihong Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zongshi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shubiao Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lvbo Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dongliang Liu.

About this article

Cite this article

Liu, D., Hu, i., Qiao, W. et al. Synthesis and characterization of a series of carbamate-linked cationic lipids for gene delivery. Lipids 40, 839–848 (2005). https://doi.org/10.1007/s11745-005-1446-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-005-1446-5

Keywords

Search

Navigation