Skip to main content

Advertisement

SpringerLink
Log in

Varying the Unsaturation in N4,N9-Dioctadecanoyl Spermines: Nonviral Lipopolyamine Vectors for More Efficient Plasmid DNA Formulation

  • Feature Article
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Purpose

The aim of the study is to analyze the effect of varying the degree of unsaturation in synthesized N4,N9-dioctadecanoyl spermines on DNA condensation and then to compare their transfection efficiency in cell culture.

Methods

The N4,N9-di-C18 lipopolyamines—saturated (stearoyl), C9-cis- (oleoyl), and C9,12-di-cis- (linoleoyl)—were synthesized from the naturally occurring polyamine spermine. The ability of these novel compounds to condense DNA and form nanoparticles was studied using ethidium bromide fluorescence quenching and nanoparticle characterization techniques. Transfection efficiency was studied in several primary skin cells (FEK4, FCP4, FCP5, FCP7, and FCP8) and in an immortalized cancer cell line (HtTA) and was compared with the commercially available nonliposomal transfection formulation Transfectam® (dioctadecylamidoglycyl spermine), which also contains two saturated C18 lipid chains.

Results

N4,N9-Dilinoleoyl spermine (C18, di-cis-9,12) is efficient at circular plasmid DNA (pEGFP) condensation and gives the most effective transfection in a series of primary skin cells and cancer cell lines at low charge ratios of 5.5 (± ammonium/phosphate).

Conclusions

The dienoic fatty acyl spermine conjugate N4,N9-dilinoleoyl spermine efficiently condenses DNA and achieves the highest transfection levels among the studied lipopolyamines in cultured cells.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

DOGS:

dioctadecylamidoglycyl spermine

DOPC:

dioleoylphosphatidyl choline

DOPE:

dioleoylphosphatidyl ethanolamine

EGFP:

enhanced green fluorescent protein

EMEM:

Earle's Minimal Essential Medium

EthBr:

ethidium bromide

FCS:

fetal calf serum

HRMS:

high-resolution mass spectroscopy

NVGT:

nonviral gene therapy

PE:

phosphatidyl ethanolamine

PLL:

poly-l-lysine

References

  1. N. Somia I. M. Verma (2000) ArticleTitleGene therapy: trials and tribulations Nat. Rev., Genet. 1 91–99 Occurrence Handle10.1038/35038533 Occurrence Handle1:CAS:528:DC%2BD3cXosFCksbs%3D

    Article  CAS  Google Scholar 

  2. H. Nakai E. Montini S. Fuess T. A. Storm M. Grompe M. A. Kay (2003) ArticleTitleAAV serotype 2 vectors preferentially integrate into active genes in mice Nat. Genet. 34 297–302 Occurrence Handle10.1038/ng1179 Occurrence Handle1:CAS:528:DC%2BD3sXkvFSrs70%3D Occurrence Handle12778174

    Article  CAS  PubMed  Google Scholar 

  3. E. Check (2003) ArticleTitleHarmful potential of viral vectors fuels doubts over gene therapy Nature 423 573–574 Occurrence Handle1:CAS:528:DC%2BD3sXkt1yktLw%3D Occurrence Handle12789298

    CAS  PubMed  Google Scholar 

  4. A. J. Geall M. A. W. Eaton T. Baker C. Catterall I. S. Blagbrough (1999) ArticleTitleThe regiochemical distribution of positive charges along cholesterol polyamine carbamates plays significant roles in modulating DNA binding affinity and lipofection FEBS Lett. 459 337–342 Occurrence Handle10.1016/S0014-5793(99)01262-4 Occurrence Handle1:CAS:528:DyaK1MXmvVKjs7o%3D Occurrence Handle10526161

    Article  CAS  PubMed  Google Scholar 

  5. I. S. Blagbrough D. Al-Hadithi A. J. Geall (2000) ArticleTitleCheno-, urso- and deoxycholic acid spermine conjugates: relative binding affinities for calf thymus DNA Tetrahedron 56 3439–3447 Occurrence Handle10.1016/S0040-4020(00)00265-9 Occurrence Handle1:CAS:528:DC%2BD3cXjsleltbo%3D

    Article  CAS  Google Scholar 

  6. A. J. Geall R. J. Taylor M. E. Earll M. A. W. Eaton I. S. Blagbrough (2000) ArticleTitleSynthesis of cholesteryl polyamine carbamates: pK(a) studies and condensation of calf thymus DNA Bioconjug. Chem. 11 314–326 Occurrence Handle10.1021/bc990115w Occurrence Handle1:CAS:528:DC%2BD3cXitlKnt7w%3D Occurrence Handle10821647

    Article  CAS  PubMed  Google Scholar 

  7. A. J. Geall D. Al-Hadithi I. S. Blagbrough (2002) ArticleTitleEfficient calf thymus DNA condensation upon binding with novel bile acid polyamine amides Bioconjug. Chem. 13 481–490 Occurrence Handle10.1021/bc000093+ Occurrence Handle1:CAS:528:DC%2BD38XjtFahtrk%3D Occurrence Handle12009937

    Article  CAS  PubMed  Google Scholar 

  8. I. S. Blagbrough A. J. Geall A. P. Neal (2003) ArticleTitlePolyamines and novel polyamine conjugates interact with DNA in ways that can be exploited in non-viral gene therapy Biochem. Soc. Trans. 31 397–406 Occurrence Handle10.1042/BST0310397 Occurrence Handle1:CAS:528:DC%2BD3sXisFGjtrY%3D Occurrence Handle12653647

    Article  CAS  PubMed  Google Scholar 

  9. A. J. Geall I. S. Blagbrough (2000) ArticleTitleHomologation of polyamines in the rapid synthesis of lipospermine conjugates and related lipoplexes Tetrahedron 56 2449–2460 Occurrence Handle10.1016/S0040-4020(99)01082-0 Occurrence Handle1:CAS:528:DC%2BD3cXislyluro%3D

    Article  CAS  Google Scholar 

  10. I. S. Blagbrough N. Adjimatera O. A. A. Ahmed A. P. Neal C. Pourzand (2004) Spermine and lipopolyamines as gene delivery agents. In D. J. Beadle, I. R. Mellor, and P. N. R. Usherwood (eds.), D. J. Beadle I. R. Mellor P. N. R. Usherwood (Eds) Neurotox '03: Neurotoxicological targets from Functional Genomics and Proteomics SCI London 147–159

    Google Scholar 

  11. O. A. A. Ahmed N. Adjimatera C. Pourzand I. S. Blagbrough (2005) ArticleTitleN4,N9-dioleoyl spermine is a novel nonviral lipopolyamine vector for plasmid DNA formulation Pharm. Res. 22 972–980 Occurrence Handle10.1007/s11095-005-4592-1 Occurrence Handle1:CAS:528:DC%2BD2MXltVKntbg%3D Occurrence Handle15948041

    Article  CAS  PubMed  Google Scholar 

  12. V. W. Y. Lui Y. K. He L. Falo L. Huang (2002) ArticleTitleSystemic administration of naked DNA encoding interleukin 12 for the treatment of human papillomavirus DNA-positive tumor Hum. Gene Ther. 13 177–185 Occurrence Handle10.1089/10430340252769716 Occurrence Handle1:CAS:528:DC%2BD38XhtFGnsL4%3D Occurrence Handle11812275

    Article  CAS  PubMed  Google Scholar 

  13. T. Kitagawa T. Iwazawa P. D. Robbins M. T. Lotze H. Tahara (2003) ArticleTitleAdvantages and limitations of particle-mediated transfection (gene gun) in cancer immuno-gene therapy using IL-10, IL-12 or B7-1 in murine tumor models J. Gene Med. 5 958–965 Occurrence Handle10.1002/jgm.441 Occurrence Handle1:CAS:528:DC%2BD3sXhtVSltr%2FJ Occurrence Handle14601133

    Article  CAS  PubMed  Google Scholar 

  14. M. Thomas A. M. Klibanov (2003) ArticleTitleConjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells Proc. Natl. Acad. Sci. USA 100 9138–9143 Occurrence Handle10.1073/pnas.1233634100 Occurrence Handle1:CAS:528:DC%2BD3sXmtlyksLY%3D Occurrence Handle12886020

    Article  CAS  PubMed  Google Scholar 

  15. A. L. Coulberson N. V. Hud J. M. Ledoux I. D. Vilfan M. R. Prausnitz (2003) ArticleTitleGene packaging with lipids, peptides and viruses inhibits transfection by electroporation in vitro J. Control. Release 86 361–370 Occurrence Handle10.1016/S0168-3659(02)00417-0 Occurrence Handle1:CAS:528:DC%2BD3sXms1Cr Occurrence Handle12526831

    Article  CAS  PubMed  Google Scholar 

  16. A. Noguchi N. Hirashima M. Nakanishi (2002) ArticleTitleCationic cholesterol promotes gene transfection using the nuclear localization signal in protamine Pharm. Res. 19 933–938 Occurrence Handle10.1023/A:1016449902541 Occurrence Handle1:CAS:528:DC%2BD38Xltl2is7Y%3D Occurrence Handle12180544

    Article  CAS  PubMed  Google Scholar 

  17. K. Fabio J. Gaucheron C. Giorgio ParticleDi P. Vierling (2003) ArticleTitleNovel galactosylated polyamine bolaamphiphiles for gene delivery Bioconjug. Chem. 14 358–367 Occurrence Handle10.1021/bc025645y Occurrence Handle1:CAS:528:DC%2BD3sXht1Oiurc%3D Occurrence Handle12643746

    Article  CAS  PubMed  Google Scholar 

  18. S. A. Cryan C. M. O'Driscoll (2003) ArticleTitleMechanistic studies on nonviral gene delivery to the intestine using in vitro differentiated cell culture models and an in vivo rat intestinal loop Pharm. Res. 20 569–575 Occurrence Handle10.1023/A:1023286413666 Occurrence Handle1:CAS:528:DC%2BD3sXivVWksb4%3D Occurrence Handle12739763

    Article  CAS  PubMed  Google Scholar 

  19. E. Wagner (2004) ArticleTitleStrategies to improve DNA polyplexes for in vivo gene transfer: will “artificial viruses” be the answer? Pharm. Res. 21 8–14 Occurrence Handle10.1023/B:PHAM.0000012146.04068.56 Occurrence Handle1:CAS:528:DC%2BD2cXkt1OmsQ%3D%3D Occurrence Handle14984252

    Article  CAS  PubMed  Google Scholar 

  20. M. Thomas Q. Ge J. J. Lu J. Z. Chen A. M. Klibanov (2005) ArticleTitleCross-linked small polyethylenimines: while still nontoxic, deliver DNA efficiently to mammalian cells in vitro and in vivo Pharm. Res. 22 373–380 Occurrence Handle10.1007/s11095-004-1874-y Occurrence Handle1:CAS:528:DC%2BD2MXivVKhtLs%3D Occurrence Handle15835742

    Article  CAS  PubMed  Google Scholar 

  21. G. Zuber E. Dauty M. Nothisen P. Belguise J. P. Behr (2001) ArticleTitleTowards synthetic viruses Adv. Drug Deliv. Rev. 52 245–253 Occurrence Handle10.1016/S0169-409X(01)00213-7 Occurrence Handle1:CAS:528:DC%2BD3MXosFKltbw%3D Occurrence Handle11718949

    Article  CAS  PubMed  Google Scholar 

  22. T. Niidome L. Huang (2002) ArticleTitleGene therapy progress and prospects: nonviral vectors Gene Ther. 9 1647–1652 Occurrence Handle10.1038/sj.gt.3301923 Occurrence Handle1:CAS:528:DC%2BD38XptFCisbo%3D Occurrence Handle12457277

    Article  CAS  PubMed  Google Scholar 

  23. M. Thomas A. M. Klibanov (2003) ArticleTitleNon-viral gene therapy: polycation-mediated DNA delivery Appl. Microbiol. Biotechnol. 62 27–34 Occurrence Handle10.1007/s00253-003-1321-8 Occurrence Handle1:CAS:528:DC%2BD3sXltVWgsrg%3D Occurrence Handle12719940

    Article  CAS  PubMed  Google Scholar 

  24. J. B. Rothbard T. C. Jessop P. A. Wender (2005) ArticleTitleAdaptive translocation: the role of hydrogen bonding and membrane potential in the uptake of guanidinium-rich transporters into cells Adv. Drug Deliv. Rev. 57 495–504 Occurrence Handle10.1016/j.addr.2004.10.003 Occurrence Handle1:CAS:528:DC%2BD2MXhslWgu7g%3D Occurrence Handle15722160

    Article  CAS  PubMed  Google Scholar 

  25. S. Mehier-Humbert R. H. Guy (2005) ArticleTitlePhysical methods for gene transfer: improving the kinetics of gene delivery into cells Adv. Drug Deliv. Rev. 57 733–753 Occurrence Handle1:CAS:528:DC%2BD2MXitFertbg%3D Occurrence Handle15757758

    CAS  PubMed  Google Scholar 

  26. V. A. Bloomfield (1991) ArticleTitleCondensation of DNA by multivalent cations—considerations on mechanism Biopolymers 31 1471–1481 Occurrence Handle10.1002/bip.360311305 Occurrence Handle1:CAS:528:DyaK38XhtVWhu7g%3D Occurrence Handle1814499

    Article  CAS  PubMed  Google Scholar 

  27. O. Rosella A. Sinclair P. R. Gibson (2000) ArticleTitlePolyunsaturated fatty acids reduce non-receptor-mediated transcellular permeation of protein across a model of intestinal epithelium in vitro J. Gastroenterol. Hepatol. 15 626–631 Occurrence Handle10.1046/j.1440-1746.2000.02215.x Occurrence Handle1:CAS:528:DC%2BD3cXltFOjt74%3D Occurrence Handle10921416

    Article  CAS  PubMed  Google Scholar 

  28. Z. Siprashvili F. A. Scholl S. F. Oliver A. Adams C. H. Contag P. A. Wender P. A. Khavari (2003) ArticleTitleGene transfer via reversible plasmid condensation with cysteine-flanked, internally spaced arginine-rich peptides Hum. Gene Ther. 14 1225–1233 Occurrence Handle10.1089/104303403767740768 Occurrence Handle1:CAS:528:DC%2BD3sXmt1enu78%3D Occurrence Handle12952594

    Article  CAS  PubMed  Google Scholar 

  29. J. Rothbard P. Robbins S. Sheu S. Oliver J. Goodnough P. Wender P. Khavari (2001) ArticleTitleMolecular transporters facilitate topical protein transduction into the skin J. Invest. Dermatol. 117 955

    Google Scholar 

  30. J. B. Rothbard T. C. Jessop R. S. Lewis B. A. Murray P. A. Wender (2004) ArticleTitleRole of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cells J. Am. Chem. Soc. 126 9506–9507 Occurrence Handle10.1021/ja0482536 Occurrence Handle1:CAS:528:DC%2BD2cXlvVSktr8%3D Occurrence Handle15291531

    Article  CAS  PubMed  Google Scholar 

  31. B. Razani M. P. Lisanti (2001) ArticleTitleCaveolins and caveolae: molecular and functional relationships Exp. Cell Res. 271 36–44 Occurrence Handle10.1006/excr.2001.5372 Occurrence Handle1:CAS:528:DC%2BD3MXotVyntro%3D Occurrence Handle11697880

    Article  CAS  PubMed  Google Scholar 

  32. Y. Xu F. C. Szoka SuffixJr (1996) ArticleTitleMechanism of DNA release from cationic liposome/DNA complexes used in cell transfection Biochemistry 35 5616–5623 Occurrence Handle1:CAS:528:DyaK28XisV2jsbg%3D Occurrence Handle8639519

    CAS  PubMed  Google Scholar 

  33. A. Roosjen J. Smisterova C. Driessen J. T. Anders A. Wagenaar D. Hoekstra R. Hulst J. B. F. N. Engberts (2002) ArticleTitleSynthesis and characteristics of biodegradable pyridinium amphiphiles used for in vitro DNA delivery Eur. J. Org. Chem. 7 1271–1277

    Google Scholar 

  34. J. P. Behr B. Demeneix J. P. Loeffler J. P. Mutul (1989) ArticleTitleEfficient gene-transfer into mammalian primary endocrine-cells with lipopolyamine-coated DNA Proc. Natl. Acad. Sci. USA 86 6982–6986 Occurrence Handle1:CAS:528:DyaK3cXhvF2l Occurrence Handle2780554

    CAS  PubMed  Google Scholar 

  35. J. S. Remy C. Sirlin P. Vierling J. P. Behr (1994) ArticleTitleGene-transfer with a series of lipophilic DNA-binding molecules Bioconjug. Chem. 5 647–654 Occurrence Handle10.1021/bc00030a021 Occurrence Handle1:CAS:528:DyaK2cXmsVOgtLY%3D Occurrence Handle7873668

    Article  CAS  PubMed  Google Scholar 

  36. P. L. Felgner Y. Barenholz J. P. Behr S. H. Cheng P. Cullis L. Huang J. A. Jessee L. Seymour F. Szoka A. R. Thierry E. Wagner G. Wu (1997) ArticleTitleNomenclature for synthetic gene delivery systems Hum. Gene Ther. 8 511–512 Occurrence Handle1:CAS:528:DyaK2sXitlCmuro%3D Occurrence Handle9095402

    CAS  PubMed  Google Scholar 

  37. G. Ronsin C. Perrin P. Guedat A. Kremer P. Camilleri A. J. Kirby (2001) ArticleTitleNovel spermine-based cationic gemini surfactants for gene delivery Chem. Commun. 21 2234–2235

    Google Scholar 

  38. R. M. Tyrrell M. Pidoux (1986) ArticleTitleQuantitative differences in host cell reactivation of ultraviolet-damaged virus in human skin fibroblasts and epidermal keratinocytes cultured from the same foreskin biopsy Cancer Res. 46 2665–2669 Occurrence Handle1:STN:280:BimC1cblvFc%3D Occurrence Handle2421882

    CAS  PubMed  Google Scholar 

  39. J. L. Zhong A. Yiakouvaki P. Holley R. M. Tyrrell C. Pourzand (2004) ArticleTitleSusceptibility of skin cells to UVA-induced necrotic cell death reflects the intracellular level of labile iron J. Invest. Dermatol. 123 771–780 Occurrence Handle10.1111/j.0022-202X.2004.23419.x Occurrence Handle1:CAS:528:DC%2BD2cXot1KgsLo%3D Occurrence Handle15373784

    Article  CAS  PubMed  Google Scholar 

  40. D. Fischer T. Bieber Y. X. Li H. P. Elsasser T. Kissel (1999) ArticleTitleA novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity Pharm. Res. 16 1273–1279 Occurrence Handle10.1023/A:1014861900478 Occurrence Handle1:CAS:528:DyaK1MXlsVyntb4%3D Occurrence Handle10468031

    Article  CAS  PubMed  Google Scholar 

  41. V. A. Bloomfield (1997) ArticleTitleDNA condensation by multivalent cations Biopolymers 44 269–282 Occurrence Handle10.1002/(SICI)1097-0282(1997)44:3<269::AID-BIP6>3.0.CO;2-T Occurrence Handle1:CAS:528:DyaK1cXjs1Snu7k%3D Occurrence Handle9591479

    Article  CAS  PubMed  Google Scholar 

  42. B. Sternberg F. L. Sorgi L. Huang (1994) ArticleTitleNew structures in complex formation between DNA and cationic liposomes visualized by freeze-fracture electron microscopy FEBS Lett. 356 361–366 Occurrence Handle10.1016/0014-5793(94)01315-2 Occurrence Handle1:CAS:528:DyaK2MXis12nsLc%3D Occurrence Handle7805873

    Article  CAS  PubMed  Google Scholar 

  43. S. Feng G. Huang (2001) ArticleTitleEffects of emulsifiers on the controlled release of paclitaxel (Taxol) from nanospheres of biodegradable polymers J. Control. Release 71 53–69 Occurrence Handle10.1016/S0168-3659(00)00364-3 Occurrence Handle1:CAS:528:DC%2BD3MXhs1Wjs7Y%3D Occurrence Handle11245908

    Article  CAS  PubMed  Google Scholar 

  44. L. Ciani S. Ristori L. Calamai G. Martini (2004) ArticleTitleDOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery: zeta potential measurements and electron spin resonance spectra Biochim. Biophys. Acta, Biomembr. 1664 70–79 Occurrence Handle1:CAS:528:DC%2BD2cXlt1Wnsrk%3D

    CAS  Google Scholar 

  45. B. A. Lobo A. Davis G. Koe J. G. Smith C. R. Middaugh (2001) ArticleTitleIsothermal titration calorimetric analysis of the interaction between cationic lipids and plasmid DNA Arch. Biochem. Biophys. 386 95–105 Occurrence Handle10.1006/abbi.2000.2196 Occurrence Handle1:CAS:528:DC%2BD3MXkt1Krtw%3D%3D Occurrence Handle11361005

    Article  CAS  PubMed  Google Scholar 

  46. C. M. Wiethoff J. G. Koe G. S. Koe C. R. Middaugh (2004) ArticleTitleCompositional effects of cationic lipid/DNA delivery systems on transgene expression in cell culture J. Pharm. Sci. 93 108–123 Occurrence Handle10.1002/jps.10519 Occurrence Handle1:CAS:528:DC%2BD2cXjvFWguw%3D%3D Occurrence Handle14648641

    Article  CAS  PubMed  Google Scholar 

  47. T. Mosmann (1983) ArticleTitleRapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays J. Immunol. Methods 65 55–63 Occurrence Handle10.1016/0022-1759(83)90303-4 Occurrence Handle1:STN:280:BiuD1cbgsFE%3D Occurrence Handle6606682

    Article  CAS  PubMed  Google Scholar 

  48. C. F. Hung T. L. Hwang C. C. Chang J. Y. Fang (2005) ArticleTitlePhysicochemical characterization and gene transfection efficiency of lipid emulsions with various co-emulsifiers Int. J. Pharm. 289 197–208 Occurrence Handle10.1016/j.ijpharm.2004.11.008 Occurrence Handle1:CAS:528:DC%2BD2MXisFKhsg%3D%3D Occurrence Handle15652212

    Article  CAS  PubMed  Google Scholar 

  49. D. G. Anderson A. Akinc N. Hossain R. Langer (2005) ArticleTitleStructure/property studies of polymeric gene delivery using a library of poly(beta-amino esters) Molec. Ther. 11 426–434 Occurrence Handle1:CAS:528:DC%2BD2MXhsVOju78%3D

    CAS  Google Scholar 

  50. K. Romoren A. Aaberge G. Smistad B. J. Thu O. Evensen (2004) ArticleTitleLong-term stability of chitosan-based polyplexes Pharm. Res. 21 2340–2346 Occurrence Handle1:CAS:528:DC%2BD2MXjslyitg%3D%3D Occurrence Handle15648267

    CAS  PubMed  Google Scholar 

  51. X. Gao L. Huang (1996) ArticleTitlePotentiation of cationic liposome-mediated gene delivery by polycations Biochemistry 35 1027–1036 Occurrence Handle1:CAS:528:DyaK28XhsFKjsA%3D%3D Occurrence Handle8547238

    CAS  PubMed  Google Scholar 

  52. S. C. Smedt ParticleDe J. Demeester W. E. Hennink (2000) ArticleTitleCationic polymer based gene delivery systems Pharm. Res. 17 113–126 Occurrence Handle10751024

    PubMed  Google Scholar 

  53. J. Panyam V. Labhasetwar (2003) ArticleTitleBiodegradable nanoparticles for drug and gene delivery to cells and tissue Adv. Drug Deliv. Rev. 55 329–347 Occurrence Handle10.1016/S0169-409X(02)00228-4 Occurrence Handle1:CAS:528:DC%2BD3sXhs1Cgurw%3D Occurrence Handle12628320

    Article  CAS  PubMed  Google Scholar 

  54. S. Mansouri P. Lavigne K. Corsi M. Benderdour E. Beaumont J. C. Fernandes (2004) ArticleTitleChitosan-DNA nanoparticles as non-viral vectors in gene therapy: strategies to improve transfection efficacy Eur. J. Pharm. Biopharm. 57 1–8 Occurrence Handle1:CAS:528:DC%2BD2cXjsFaltQ%3D%3D Occurrence Handle14729076

    CAS  PubMed  Google Scholar 

  55. J. Rejman V. Oberle I. S. Zuhorn D. Hoekstra (2004) ArticleTitleSize-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis Biochem. J. 377 159–169 Occurrence Handle10.1042/BJ20031253 Occurrence Handle1:CAS:528:DC%2BD2cXis1Wnsg%3D%3D Occurrence Handle14505488

    Article  CAS  PubMed  Google Scholar 

  56. M. Ogris P. Steinlein M. Kursa K. Mechtler R. Kircheis E. Wagner (1998) ArticleTitleThe size of DNA/transferrin–PEI complexes is an important factor for gene expression in cultured cells Gene Ther. 5 1425–1433 Occurrence Handle10.1038/sj.gt.3300745 Occurrence Handle1:CAS:528:DyaK1cXms1Wmtbg%3D Occurrence Handle9930349

    Article  CAS  PubMed  Google Scholar 

  57. E. Wagner M. Cotten R. Foisner M. L. Birnstiel (1991) ArticleTitleTransferrin–polycation–DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells Proc. Natl. Acad. Sci. USA 88 4255–4259 Occurrence Handle1:CAS:528:DyaK3MXkt1elsrg%3D Occurrence Handle2034670

    CAS  PubMed  Google Scholar 

  58. G. Byk C. Dubertret V. Escriou M. Frederic G. Jaslin R. Rangara B. Pitard J. Crouzet P. Wils B. Schwartz D. Scherman (1998) ArticleTitleSynthesis, activity, and structure–activity relationship studies of novel cationic lipids for DNA transfer J. Med. Chem. 41 224–235 Occurrence Handle10.1021/jm9704964

    Article  Google Scholar 

  59. B. G. Feuerstein L. D. Williams H. S. Basu L. J. Marton (1991) ArticleTitleImplications and concepts of polyamine–nucleic acid interactions J. Cell. Biochem. 46 37–47 Occurrence Handle10.1002/jcb.240460107 Occurrence Handle1:CAS:528:DyaK3MXkt1Cnu74%3D Occurrence Handle1874798

    Article  CAS  PubMed  Google Scholar 

  60. H. Farhood N. Serbina L. Huang (1995) ArticleTitleThe role of dioleoyl phosphatidylethanolamine in cationic liposome-mediated gene-transfer Biochim. Biophys. Acta, Biomembr. 1235 289–295

    Google Scholar 

  61. B. Buchberger E. Fernholz H. v. d. Eltz M. Hinzepeter (1996) ArticleTitleDOSPER liposomal transfection reagent: a reagent with unique transfection properties Biochem. Inform. 98 27–29

    Google Scholar 

  62. J. Monkkonen A. Urtti (1998) ArticleTitleLipid fusion in oligonucleotide and gene delivery with cationic lipids Adv. Drug Deliv. Rev. 34 37–49 Occurrence Handle10.1016/S0169-409X(98)00004-0 Occurrence Handle1:CAS:528:DyaK1cXmvFWisr0%3D Occurrence Handle10837669

    Article  CAS  PubMed  Google Scholar 

  63. D. C. Litzinger L. Huang (1992) ArticleTitlePhosphatidylethanolamine liposomes—drug delivery, gene-transfer and immunodiagnostic applications Biochim. Biophys. Acta 1113 201–227 Occurrence Handle1:CAS:528:DyaK38XltlOnu7w%3D Occurrence Handle1510997

    CAS  PubMed  Google Scholar 

  64. J. Gaucheron C. Santaella P. Vierling (2001) ArticleTitleHighly fluorinated lipospermines for gene transfer: synthesis and evaluation of their in vitro transfection efficiency Bioconjug. Chem. 12 114–128 Occurrence Handle1:CAS:528:DC%2BD3MXhtlw%3D Occurrence Handle11170374

    CAS  PubMed  Google Scholar 

  65. P. Vierling C. Santaella J. G. Riess (1995) Fluorinated liposomes F. Puisieux P. Courveur J. Delattre J. P. Devissaguet (Eds) Liposomes: New Systems and New Trends in Their Application Edition de Sante Paris 293–318

    Google Scholar 

Download references

Acknowledgments

We acknowledge the financial support of an Egyptian Government studentship to O.A.A.A. We are grateful to Prof. R. M. Tyrrell (University of Bath) for FEK4 and HtTA cell lines. We also thank Dr. J. M. H. van den Elsen (University of Bath) for generous help with the particle size measurements (funded under a BBSRC grant BBS/B/12121).

Author information

Authors and Affiliations

  1. Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK

    Osama A. A. Ahmed, Charareh Pourzand & Ian S. Blagbrough

Authors
  1. Osama A. A. Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charareh Pourzand
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ian S. Blagbrough
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ian S. Blagbrough.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ahmed, O.A.A., Pourzand, C. & Blagbrough, I.S. Varying the Unsaturation in N4,N9-Dioctadecanoyl Spermines: Nonviral Lipopolyamine Vectors for More Efficient Plasmid DNA Formulation. Pharm Res 23, 31–40 (2006). https://doi.org/10.1007/s11095-005-8717-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-005-8717-3

Key Words

Search

Navigation