Liposomes pp 107-117 | Cite as

Elastic Liposomes for Topical and Transdermal Drug Delivery

  • Heather A. E. BensonEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1522)


Elastic liposomes have been developed and evaluated as novel topical and transdermal delivery systems. They share some similarities to conventional liposomes but their composition is designed to confer flexibility and elasticity in the lipid bilayer structure. Elastic liposomes are applied non-occluded to the skin and are reported to permeate through the stratum corneum lipid lamellar regions as a result of the hydration or osmotic force in the skin. They have been investigated as drug carriers for a range of small molecules, peptides, proteins, and vaccines, both in vitro and in vivo. Following topical application, structural changes in the stratum corneum have been identified and intact elastic liposomes visualized within the stratum corneum lipid lamellar regions, but evidence of intact liposomes in the deeper viable tissues is limited. The method by which they transport their drug payload into and through the skin has been investigated but remains an area of contention. This chapter provides an overview of the development, characterization, and evaluation of elastic liposomes for delivery into and via the skin.

Key words

Colloids Elastic liposomes Liposomes Transfersomes Skin penetration enhancement Drug carriers 


  1. 1.
    Cevc G, Blume G (2001) New, highly efficient formulation of diclofenac for the topical, transdermal administration in ultradeformable drug carriers, transfersomes. Biochim Biophys Acta 1514(2):191–205CrossRefPubMedGoogle Scholar
  2. 2.
    El Maghraby GM, Williams AC, Barry BW (1999) Skin delivery of oestradiol from deformable and traditional liposomes: mechanistic studies. J Pharm Pharmacol 51(10):1123–1134CrossRefPubMedGoogle Scholar
  3. 3.
    Trotta M, Peira E, Carlotti ME, Gallarate M (2004) Deformable liposomes for dermal administration of methotrexate. Int J Pharm 270(1-2):119–125CrossRefPubMedGoogle Scholar
  4. 4.
    Cevc G (2003) Transdermal drug delivery of insulin with ultradeformable carriers. Clin Pharmacokinet 42(5):461–474CrossRefPubMedGoogle Scholar
  5. 5.
    Cevc G, Blume G (1992) Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta 1104(1):226–232CrossRefPubMedGoogle Scholar
  6. 6.
    Cevc G, Mazgareanu S, Rother M (2008) Preclinical characterisation of NSAIDs in ultradeformable carriers or conventional topical gels. Int J Pharm 360(1-2):29–39CrossRefPubMedGoogle Scholar
  7. 7.
    Cevc G, Mazgareanu S, Rother M, Vierl U (2008) Occlusion effect on transcutaneous NSAID delivery from conventional and carrier-based formulations. Int J Pharm 359(1-2):190–197CrossRefPubMedGoogle Scholar
  8. 8.
    Cevc G, Vierl U, Mazgareanu S (2008) Functional characterisation of novel analgesic product based on self-regulating drug carriers. Int J Pharm 360(1-2):18–28CrossRefPubMedGoogle Scholar
  9. 9.
    Boinpally RR, Zhou SL, Poondru S, Devraj G, Jasti BR (2003) Lecithin vesicles for topical delivery of diclofenac. Eur J Pharm Biopharm 56(3):389–392CrossRefPubMedGoogle Scholar
  10. 10.
    Bouwstra JA, De Graaff A, Groenink W, Honeywell L (2002) Elastic vesicles: interaction with human skin and drug transport. Cell Mol Biol Lett 7(2):222–223PubMedGoogle Scholar
  11. 11.
    Honeywell-Nguyen PL, Gooris GS, Bouwstra JA (2004) Quantitative assessment of the transport of elastic and rigid vesicle components and a model drug from these vesicle formulations into human skin in vivo. J Invest Dermatol 123(5):902–910CrossRefPubMedGoogle Scholar
  12. 12.
    Cevc G, Schatzlein A, Blume G (1995) Transdermal drug carriers: basic properties, optimization and transfer efficiency in the case of epicutaneously applied peptides. J Control Release 36:3–16CrossRefGoogle Scholar
  13. 13.
    Cevc G (1996) Transfersomes, liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug Carrier Sys 13(3-4):257–388CrossRefGoogle Scholar
  14. 14.
    Cevc G, Schatzlein A, Richardsen H (2002) Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Evidence from double label CLSM experiments and direct size measurements. Biochim Biophys Acta 1564(1):21–30CrossRefPubMedGoogle Scholar
  15. 15.
    Honeywell-Nguyen PL, Arenja S, Bouwstra JA (2003) Skin penetration and mechanisms of action in the delivery of the D2-agonist rotigotine from surfactant-based elastic vesicle formulations. Pharm Res 20(10):1619–1625CrossRefPubMedGoogle Scholar
  16. 16.
    van den Bergh BA, Bouwstra JA, Junginger HE, Wertz PW (1999) Elasticity of vesicles affects hairless mouse skin structure and permeability. J Control Release 62(3):367–379CrossRefPubMedGoogle Scholar
  17. 17.
    van den Bergh BA, Vroom J, Gerritsen H, Junginger HE, Bouwstra JA (1999) Interactions of elastic and rigid vesicles with human skin in vitro: electron microscopy and two-photon excitation microscopy. Biochim Biophys Acta 1461(1):155–173CrossRefPubMedGoogle Scholar
  18. 18.
    Trotta M, Peira E, Debernardi F, Gallarate M (2002) Elastic liposomes for skin delivery of dipotassium glycyrrhizinate. Int J Pharm 241(2):319–327CrossRefPubMedGoogle Scholar
  19. 19.
    El Maghraby GM, Williams AC, Barry BW (2000) Oestradiol skin delivery from ultradeformable liposomes: refinement of surfactant concentration. Int J Pharm 196(1):63–74CrossRefPubMedGoogle Scholar
  20. 20.
    El Maghraby GM, Williams AC, Barry BW (2000) Skin delivery of oestradiol from lipid vesicles: importance of liposome structure. Int J Pharm 204(1-2):159–169CrossRefPubMedGoogle Scholar
  21. 21.
    Song YK, Kim CK (2006) Topical delivery of low-molecular-weight heparin with surface-charged flexible liposomes. Biomaterials 27(2):271–280CrossRefPubMedGoogle Scholar
  22. 22.
    Kirjavainen M, Urtti A, Jaaskelainen I, Suhonen TM, Paronen P, Valjakka-Koskela R et al (1996) Interaction of liposomes with human skin in vitro—the influence of lipid composition and structure. Biochim Biophys Acta 1304(3):179–189CrossRefPubMedGoogle Scholar
  23. 23.
    Geusens B, Lambert J, De Smedt SC, Buyens K, Sanders NN, Van Gele M (2009) Ultradeformable cationic liposomes for delivery of small interfering RNA (siRNA) into human primary melanocytes. J Control Release 133(3):214–220CrossRefPubMedGoogle Scholar
  24. 24.
    Geusens B, Van Gele M, Braat S, De Smedt SC, Stuart MC, Prow TW et al (2010) Flexible nanosomes (SECosomes) enable efficient siRNA delivery in cultured primary skin cells and in the viable epidermis of ex vivo human skin. Adv Funct Mater 20(23):4077–4090CrossRefGoogle Scholar
  25. 25.
    El Maghraby GM, Williams AC, Barry BW (2004) Interactions of surfactants (edge activators) and skin penetration enhancers with liposomes. Int J Pharm 276(1-2):143–161CrossRefPubMedGoogle Scholar
  26. 26.
    Mura S, Manconi M, Sinico C, Valenti D, Fadda AM (2009) Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil. Int J Pharm 380(1-2):72–79CrossRefPubMedGoogle Scholar
  27. 27.
    Manconi M, Sinico C, Caddeo C, Vila AO, Valenti D, Fadda AM (2011) Penetration enhancer containing vesicles as carriers for dermal delivery of tretinoin. Int J Pharm 412(1-2):37–46CrossRefPubMedGoogle Scholar
  28. 28.
    Manconi M, Caddeo C, Sinico C, Valenti D, Mostallino MC, Lampis S et al (2012) Penetration enhancer-containing vesicles: composition dependence of structural features and skin penetration ability. Eur J Pharm Biopharm 82(2):352–359CrossRefPubMedGoogle Scholar
  29. 29.
    Cevc G, Blume G, Schatzlein A (1997) Transfersomes-mediated transepidermal delivery improves the regio-specificity and biological activity of corticosteroids in vivo. J Control Release 45(3):211–226CrossRefGoogle Scholar
  30. 30.
    Honeywell-Nguyen PL, Bouwstra JA (2003) The in vitro transport of pergolide from surfactant-based elastic vesicles through human skin: a suggested mechanism of action. J Control Release 86(1):145–156CrossRefPubMedGoogle Scholar
  31. 31.
    Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM (2006) Deformable liposomes and ethosomes: mechanism of enhanced skin delivery. Int J Pharm 322(1-2):60–66CrossRefPubMedGoogle Scholar
  32. 32.
    Dubey V, Mishra D, Asthana A, Jain NK (2006) Transdermal delivery of a pineal hormone: melatonin via elastic liposomes. Biomaterials 27(18):3491–3496CrossRefPubMedGoogle Scholar
  33. 33.
    Fry DW, White JC, Goldman ID (1978) Rapid separation of low molecular weight solutes from liposomes without dilution. Anal Biochem 90(2):809–815CrossRefPubMedGoogle Scholar
  34. 34.
    Kligman A, Christophers E (1963) Preparation of isolated sheets of human stratum corneum. Arch Dermatol 88:70–73CrossRefGoogle Scholar
  35. 35.
    Konig K, Raphael AP, Lin L, Grice JE, Soyer HP, Breunig HG et al (2011) Applications of multiphoton tomographs and femtosecond laser nanoprocessing microscopes in drug delivery research. Adv Drug Deliv Rev 63(4-5):388–404CrossRefPubMedGoogle Scholar
  36. 36.
    Roberts MS, Dancik Y, Prow TW, Thorling CA, Lin LL, Grice JE et al (2011) Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy. Eur J Pharm Biopharm 77(3):469–488CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.School of Pharmacy, Curtin Health Innovation Research InstituteCurtin UniversityPerthAustralia

Personalised recommendations