Nanovesicles for Nanomedicine: Theory and Practices

  • Sheetu Wadhwa
  • Varun Garg
  • Monica Gulati
  • Bhupinder Kapoor
  • Sachin Kumar Singh
  • Neeraj Mittal
Part of the Methods in Molecular Biology book series (MIMB, volume 2000)


Lipid-based nanovesicles such as liposomes, niosomes, and ethosomes are now well recognized as potential candidates for drug delivery and theranostic applications. Some of them have already stepped forward from laboratory to market. The property to entrap lipophilic drugs in their bilayers and hydrophilic drugs in the aqueous milieu makes them a unique carrier for drug delivery. Delivery of drugs/diagnostics to various organs/tissues/cells via nanovesicles is considered to be a topic of long-standing interest with new challenges being posed to formulation scientists with new developments. The key challenge in this context is the physiological and pathological conditions, which make the delivery of drugs extremely difficult at the disease locus and makes their precise delivery ineffective. This chapter gives an insight into the role of novel nanovesicles in the field of drug delivery. We present an overview of the formulation and characterization and role of diverse nanovesicles. A comprehensive update about their application and current as well as potential challenges have also been discussed.

Key words

Nanovesicles Topical Transdermal Lipid-based Drug delivery 


  1. 1.
    Cevc G (2004) Lipid vesicles and other colloids as drug carriers on the skin. Adv Drug Deliv Rev 56:675–711CrossRefGoogle Scholar
  2. 2.
    Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13:238–252CrossRefGoogle Scholar
  3. 3.
    Barry BW (2002) Drug delivery routes in skin: a novel approach. Adv Drug Deliv Rev 54:S31–S40CrossRefGoogle Scholar
  4. 4.
    Bangham AD, Standish MM, Watkins JC et al (1967) The diffusion of ions from a phospholipid model membrane system. Protoplasma 63:183–187CrossRefGoogle Scholar
  5. 5.
    Papahadjopoulos D, Watkins JC (1967) Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals. Biochim Biophys Acta 135:639–652CrossRefGoogle Scholar
  6. 6.
    Deamer DW (2010) From “Banghasomes” to liposomes: a memoir of Alec Bangham, 1921–2010. FASEB J 24:1308–1310CrossRefGoogle Scholar
  7. 7.
    Batzri S, Korn ED (1973) Single bilayer liposomes prepared without sonication. Biochim Biophys Acta 298:1015–1019CrossRefGoogle Scholar
  8. 8.
    Gregoriadis G, Ryman BE (1971) Liposomes as carriers of enzymes or drugs: a new approach to the treatment of storage diseases. Biochem J 124:58PCrossRefGoogle Scholar
  9. 9.
    Gregoriadis G (1973) Drug entrapment in liposomes. FEBS Lett 36:292–296CrossRefGoogle Scholar
  10. 10.
    Gregoriadis G (1976) The carrier potential of liposomes in biology and medicine. Part 1. N Engl J Med 295:704–710CrossRefGoogle Scholar
  11. 11.
    Gregoriadis G (1976) The carrier potential of liposomes in biology and medicine. Part 2. N Engl J Med 295:765–770CrossRefGoogle Scholar
  12. 12.
    Biju SS, Talegaonkar S, Mishra PR et al (2006) Vesicular systems: an overview. Indian J Pharm Sci 68:141–153CrossRefGoogle Scholar
  13. 13.
    Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4:145–160CrossRefGoogle Scholar
  14. 14.
    Kajimoto K, Yamamoto M, Watanabe M et al (2011) Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis. Int J Pharm 403:57–65CrossRefGoogle Scholar
  15. 15.
    Honeywell-Nguyen PL, Bouwstra JA (2005) Vesicles as a tool for transdermal and dermal delivery. Drug Discov Today Technol 2:67–74CrossRefGoogle Scholar
  16. 16.
    Redziniak G (2003) Liposomes et peau: passé, présent, futur. Pathol Biol 51:279–281CrossRefGoogle Scholar
  17. 17.
    Uchegbu IF, Vyas SP (1998) Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm 172:33–70CrossRefGoogle Scholar
  18. 18.
    Uchegbu I (1998) The biodistribution of novel 200-nm palmitoyl muramic acid vesicles. Int J Pharm 162:19–27CrossRefGoogle Scholar
  19. 19.
    Cevc G, Blume G (2004) Hydrocortisone and dexamethasone in very deformable drug carriers have increased biological potency, prolonged effect, and reduced therapeutic dosage. Biochim Biophys Acta 1663:61–73CrossRefGoogle Scholar
  20. 20.
    Cevc G, Mazgareanu S, Rother M (2008) Preclinical characterisation of NSAIDs in ultradeformable carriers or conventional topical gels. Int J Pharm 360:29–39CrossRefGoogle Scholar
  21. 21.
    Rahman YE, Rosenthal MW, Cerny EA et al (1974) Preparation and prolonged tissue retention of liposome-encapsulated chelating agents. J Lab Clin Med 83:640–647PubMedGoogle Scholar
  22. 22.
    Jain S, Jain NK (2008) Liposomes as drug carriers. In: Jain NK (ed) Controlled and novel drug delivery, 1st edn. CBS Publisher and Distributors, New Delhi, pp 304–352Google Scholar
  23. 23.
    Patel R, Singh SK, Singh S et al (2009) Development and characterization of curcumin loaded transfersome for transdermal delivery. J Pharm Sci Res 1:71–80Google Scholar
  24. 24.
    Vyas SP, Khar RK (2008) Targeted and controlled drug delivery, 1st edn. CBS Publishers and Distributors, New DelhiGoogle Scholar
  25. 25.
    Cevc G, Schätzlein 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 1564:21–30CrossRefGoogle Scholar
  26. 26.
    Trotta M, Peira E, Debernardi F et al (2002) Elastic liposomes for skin delivery of dipotassium glycyrrhizinate. Int J Pharm 241:319–327CrossRefGoogle Scholar
  27. 27.
    Barry BW (2001) Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci 14:101–114CrossRefGoogle Scholar
  28. 28.
    van den Bergh BA, Vroom J, Gerritsen H et al (1999) Interactions of elastic and rigid vesicles with human skin in vitro: electron microscopy and two-photon excitation microscopy. Biochim Biophys Acta 1461:155–173CrossRefGoogle Scholar
  29. 29.
    Cevc G, Gebauer D, Stieber J et al (1998a) Ultraflexible vesicles, transfersomes, have an extremely low pore penetration resistance and transport therapeutic amounts of insulin across the intact mammalian skin. Biochim Biophys Acta 1368:201–215CrossRefGoogle Scholar
  30. 30.
    Goosen C, Du Plessis J, Müller DG et al (1998b) Correlation between physicochemical characteristics, pharmacokinetic properties and transdermal absorption of NSAID’s. Int J Pharm 163:203–209CrossRefGoogle Scholar
  31. 31.
    Oh EK, Jin SE, Kim JK et al (2011) Retained topical delivery of 5-aminolevulinic acid using cationic ultradeformable liposomes for photodynamic therapy. Eur J Pharm Sci 44:149–157CrossRefGoogle Scholar
  32. 32.
    Sheo DM, Shweta A, Ram CD et al (2010) Transfersomes-A novel vesicular carrier for enhanced transdermal delivery of stavudine: development, characterization and performance evaluation. J Sci Speculat Res 1:30–36Google Scholar
  33. 33.
    Trotta M, Peira E, Carlotti ME (2004) Deformable liposomes for dermal administration of methotrexate. Int J Pharm 270:119–125CrossRefGoogle Scholar
  34. 34.
    El Zaafarany GM, Awad GA, Holayel SM et al (2010) Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery. Int J Pharm 397:164–172CrossRefGoogle Scholar
  35. 35.
    Kim A, Lee EH, Choi SH et al (2004) In vitro and in vivo transfection efficiency of a novel ultradeformable cationic liposome. Biomaterials 25:305–313CrossRefGoogle Scholar
  36. 36.
    Lau KG, Hattori Y, Chopra S et al (2005) Ultra-deformable liposomes containing bleomycin: in vitro stability and toxicity on human cutaneous keratinocyte cell lines. Int J Pharm 300:4–12CrossRefGoogle Scholar
  37. 37.
    Cevc G, Blume G (1992) Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta 1104:226–232CrossRefGoogle Scholar
  38. 38.
    Cevc G, Gebauer D (2003) Hydration-driven transport of deformable lipid vesicles through fine pores and the skin barrier. Biophys J 84:1010–1024CrossRefGoogle Scholar
  39. 39.
    Bendas ER, Tadros MI (2007) Enhanced transdermal delivery of salbutamol sulfate via ethosomes. AAPS PharmSciTech 8:213–220CrossRefGoogle Scholar
  40. 40.
    Touitou E, Dayan N, Bergelson L et al (2000) Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release 65:403–418CrossRefGoogle Scholar
  41. 41.
    Upadhyay N, Mandal S, Bhatia L et al (2011) A review on ethosomes: an emerging approach for drug delivery through the skin. Rec Res Sci Tech 3:19–24Google Scholar
  42. 42.
    New RRC (1999) Liposomes a practical approach, 1st edn. Oxford University Press, New YorkGoogle Scholar
  43. 43.
    Laouini A, Jaafar-Maalej C, Limayem-Blouza I et al (2012) Preparation, characterization and applications of liposomes: state of the art. J Colloid Sci Biotechnol 1(2):147–168CrossRefGoogle Scholar
  44. 44.
    Verma P, Pathak K (2012) Nanosized ethanolic vesicles loaded with econazole nitrate for the treatment of deep fungal infections through topical gel formulation. Nanomedicine 8:489–496CrossRefGoogle Scholar
  45. 45.
    Chen Y, Lu Y, Chen J et al (2009) Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using liposomes containing a bile salt. Int J Pharm 376:153–160CrossRefGoogle Scholar
  46. 46.
    Agronskia A, Valentijn J, Driel L et al (2008) Integrated fluoroscense and transmission electron microscopy. J Struct Biol 164:183–189CrossRefGoogle Scholar
  47. 47.
    Parry K (2000) Scanning electron microscopy: an introduction. Ill-Vs Rev 13:40–44Google Scholar
  48. 48.
    Dragovic R, Gardiner C, Brooks A et al (2011) Sizing and phenotyping of cellular vesicles using nanoparticle tracking analysis. Nanomedicine 7:780–788CrossRefGoogle Scholar
  49. 49.
    Kato H, Suzuki M, Fuzita K (2009) Reliable size determination of nanoparticles using dynamic light scattering method for in vitro toxicology accessment. Toxicol In Vitro 23:927–934CrossRefGoogle Scholar
  50. 50.
    Fan H, Nazari M, Raval G (2014) Utilizing zeta potential to study the effective charge, membrane partitioning and membrane permeation of lipopeptide surfactine. Biochim Biophys Acta 1838:2306–2312CrossRefGoogle Scholar
  51. 51.
    Marsalek R (2014) Particle size and zeta potential of ZnO. APCBEE Procedia 9:13–17CrossRefGoogle Scholar
  52. 52.
    Demetzos C (2008) Differential scanning calorimetry (DSC): a tool to study the thermal behavior of lipid bilayers and liposomal stability. J Liposome Res 18(3):159–173CrossRefGoogle Scholar
  53. 53.
    Song YK, Kim CK (2006) Topical delivery of low-molecular-weight heparin with surface-charged flexible liposomes. Biomaterials 27:271–280CrossRefGoogle Scholar
  54. 54.
    Gillet A, Lecomte F, Hubert P et al (2011) Skin penetration behaviour of liposomes as a function of their composition. Eur J Pharm Biopharm 79:43–53CrossRefGoogle Scholar
  55. 55.
    Ascenso A, Raposo S, Batista C et al (2015) Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes. Int J Nanomedicine 10:5837–5851CrossRefGoogle Scholar
  56. 56.
    Garg V, Singh H, Bimbrawh S et al (2017) Ethosomes and transfersomes: principles, perspectives and practices. Curr Drug Deliv 14:613–633. Scholar
  57. 57.
    Sharma R, Yasir M (2010) Virosomes: a novel carrier for drug delivery. Int J Pharm Tech Res 2:2327–2339Google Scholar
  58. 58.
    Saroja CH, Lakshmi PK, Bhaskaran S (2011) Recent trends in vaccine delivery systems: a review. Int J Pharm Invest 1:64–74CrossRefGoogle Scholar
  59. 59.
    Biju SS, Sushama T, Mishra PR, Khar RK (2006) Vesicular systems: An overview. Indian J Pharm Sci. 68:141–153CrossRefGoogle Scholar
  60. 60.
    Patel RP, Patel H, Baria AH (2009) Formulation and evaluation of liposomes of ketoconazole. Int J Drug Deliv Technol 1:16–23Google Scholar
  61. 61.
    Ahmad J, Singhal M, Amin S, Rizwanullah M, Akhter S, Kamal MA, Haider N, Midoux P, Pichon C (2017) Bile salt stabilized vesicles (Bilosomes): a novel nano-pharmaceutical design for oral delivery of proteins and peptides. Curr Pharm Des 23:1575–1588CrossRefGoogle Scholar
  62. 62.
    Paliwal R, Paliwal SR, Mishra N, Mehta A, Vyas SP (2009) Engineered chylomicron mimicking carrier emulsome for lymph targeted oral delivery of methotrexate. Int J Pharm 380:181–188CrossRefGoogle Scholar
  63. 63.
    Shivhare UD, Ambulkar DU, Mathur VB et al (2009) Formulation and evaluation of pentoxifylline liposome formulation. Dig J Nanomater Biostruct 4:857–862Google Scholar
  64. 64.
    Lasic DD, Papahadjopoulos D (eds) (1998) Applications of liposomes. Elsevier, AmsterdamGoogle Scholar
  65. 65.
    Kirpotin DB, Lasic DD, Papahadjopoulos D (1998) Medical applications of liposomes. Elsevier, AmsterdamGoogle Scholar
  66. 66.
    Posner R (2002) Liposomes. J Drugs Dermatol 1:161–164PubMedGoogle Scholar
  67. 67.
    Conacher M, Alexander J, Brewer JM (2000) Niosomes as immunological adjuvants. In: Uchegbu IF (ed) Synthetic surfactant vesicles. International Publishers Distributors Ltd, Singapore, pp 185–205Google Scholar
  68. 68.
    Malhotra M, Jain NK (1994) Niosomes as drug carriers. Indian Drugs 31:81–86Google Scholar
  69. 69.
    Kazi KM, Mandal AS, Biswas N et al (2010) Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res 1:374–380CrossRefGoogle Scholar
  70. 70.
    Hafer C, Goble R, Deering P et al (1999) Formulation of interleukin-2 and interferon-alpha containing ultra deformable carriers for potential transdermal application. Anticancer Res 19:1505–1507Google Scholar
  71. 71.
    Duangjit S, Opanasopit P, Rojanarata T et al (2011) Characterization and in vitro skin permeation of meloxicam-loaded liposomes versus transfersomes. J Drug Deliv 2011:418316. Scholar
  72. 72.
    Cevc G (1996) Transferosomes, liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug Carrier Syst 13:257–388CrossRefGoogle Scholar
  73. 73.
    Dkeidek I, Touitou E (1999) Ethosomes: a recent approach in transdermal/topical delivery. AAPS Pharm Sci 1:202Google Scholar
  74. 74.
    Ehab R, Bendas L, Mina I (2007) Enhanced transdermal delivery of salbutamol sulfate via ethosomes. AAPS PharmSciTech 8:213–220CrossRefGoogle Scholar
  75. 75.
    Vyas SP, Khar RK (2002) Targeted and controlled drug delivery. CBS publisher, New DelhiGoogle Scholar
  76. 76.
    Lankalapalli S, Damuluri M (2012) Sphingosomes: applications in targeted drug delivery. Int J Pharm Chem Biol Sci 2:507–516Google Scholar
  77. 77.
    Saraf S, Gupta D, Kaur CD et al (2011) Sphingosomes a novel approach to vesicular drug delivery. Int J Curr Sci Res 1:63–68Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sheetu Wadhwa
    • 1
  • Varun Garg
    • 1
  • Monica Gulati
    • 1
  • Bhupinder Kapoor
    • 1
  • Sachin Kumar Singh
    • 1
  • Neeraj Mittal
    • 2
  1. 1.School of Pharmaceutical SciencesLovely Professional UniversityPhagwaraIndia
  2. 2.Department of Pharmaceutical Sciences and Drug ResearchPunjabi UniversityPatialaIndia

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