Skip to main content
PMC home page
AAPS PharmSciTech logoLink to AAPS PharmSciTech
. 2007 Jul 18;8(4):249. doi: 10.1208/pt0804111

Formulation and evaluation of ethosomes for transdermal delivery of lamivudine

Subheet Jain 1,✉, Ashok K Tiwary 1, Bharti Sapra 1, Narendra K Jain 2
PMCID: PMC2750697  PMID: 18181532

Abstract

The purpose of the present research was to investigate the mechanism for improved intercellular and intracellular drug delivery from ethosomes using visualization techniques and cell line study. Ethosomal formulations were prepared using lamivudine as model drug and characterized in vitro, ex vivo and in vivo. Transmission electron microscopy, scanning electron microscopy, and fluorescence microscopy were employed to determine the effect of ethosome on ultrastructure of skin. Cytotoxicity and cellular uptake of ethosome were determined using T-lymphoid cell line (MT-2). The optimized ethosomal formulation showed 25 times higher transdermal flux (68.4±3.5 µg/cm2/h) across the rat skin as compared with that of lamivudine solution (2.8±0.2 µg/cm2/h). Microscopic studies revealed that ethosomes influenced the ultrastructure of stratum corneum. Distinct regions with lamellar stacks derived from vesicles were observed in intercellular region of deeper skin layers. Results of cellular uptake study showed significantly higher intracellular uptake of ethosomes (85.7%±4.5%) as compared with drug solution (24.9%±1.9%). The results of the characterization studies indicate that lipid perturbation along with elasticity of ethosomes vesicles seems to be the main contributor for improved skin permeation.

Keywords: Ethosomes, skin, transmission electron microscopy, scanning electron microscopy, fluorescence microscopy, cell line study

Full Text

The Full Text of this article is available as a PDF (497.0 KB).

Footnotes

December 21, 2007

References

  • 1.Jarvis B, Faulds D. Lamivudine: a review of its therapeutic potential in chronic hepatitis B. Drugs. 1999;58:101–141. doi: 10.2165/00003495-199958010-00015. [DOI] [PubMed] [Google Scholar]
  • 2.Dutta T, Jain NK. Targeting potential and anti-HIV activity of lamivudine-loaded mannosylated poly(propyleneimine) dendrimer. Biochim Biophys Acta. 2007;1770:681–686. doi: 10.1016/j.bbagen.2006.12.007. [DOI] [PubMed] [Google Scholar]
  • 3.Schreier H, Bouwstra J. Liposomes and niosomes as a drug carriers: dermal and transdermal drug delivery. J Control Release. 1994;30:1–15. doi: 10.1016/0168-3659(94)90039-6. [DOI] [Google Scholar]
  • 4.Cevc G, Blume G, Schatzlein A, Gebauer D, Paul A. The skin: a pathway for the systemic treatment with patches and lipid based agent carriers. Adv Drug Deliv Rev. 1996;18:349–378. doi: 10.1016/0169-409X(95)00091-K. [DOI] [Google Scholar]
  • 5.Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release. 2000;65:403–418. doi: 10.1016/S0168-3659(99)00222-9. [DOI] [PubMed] [Google Scholar]
  • 6.Touitou E, inventor. Composition of applying active substance to or through the skin. US patent 5 540 934. July 30, 1996.
  • 7.Touitou E, inventor. Composition of applying active substance to or through the skin. US patent 5 716 638. October 2, 1998.
  • 8.Touitou E, Godin B, Dayan N, Weiss C, Piliponsky A, Levi-Schaffer F. Intracellular delivery mediated by an ethosomal carrier. Biomaterials. 2001;22:3053–3059. doi: 10.1016/S0142-9612(01)00052-7. [DOI] [PubMed] [Google Scholar]
  • 9.Jain S, Umamaheshwari RB, Bhadra D, Jain NK. Ethosomes: a novel vesicular carrier for enhanced transdermal delivery of an anti-HIV agent. Ind J Pharma Sci. 2004;66:72–81. [Google Scholar]
  • 10.Bangham AD, Standish MM, Watkins JC. The action of steroids and streptolysin S on the permeability of phospholipid structures to cations. J Mol Biol. 1965;13:253–259. doi: 10.1016/S0022-2836(65)80094-8. [DOI] [PubMed] [Google Scholar]
  • 11.Lopez-Pinto JM, Gonzalez-Rodriguez ML, Robasco AM. Effect of cholesterol and ethanol on dermal delivery of DPPC liposome. Int J Pharm. 2005;298:1–12. doi: 10.1016/j.ijpharm.2005.02.021. [DOI] [PubMed] [Google Scholar]
  • 12.Jain S, Jain P, Jain NK. Transfersomes: a novel vesicular carrier for enhanced transdermal delivery: development, characterization and performance evaluation. Drug Dev Ind Pharm. 2003;29:1013–1026. doi: 10.1081/DDC-120025458. [DOI] [PubMed] [Google Scholar]
  • 13.Jain S, Jain N, Bhadra D, Tiwary AK, Jain NK. Transdermal delivery of an analgesic agent using elastic liposomes: preparation, characterization and performance evaluation. Curr Drug Deliv. 2005;2:223–233. doi: 10.2174/1567201054368020. [DOI] [PubMed] [Google Scholar]
  • 14.Bedoya LM, Sanchez-Palomino S, Abad MJ, Bermejo P, Alcami J. Anti-HIV activity of medicinal plant extracts. J Ethnopharmacol. 2001;77:113–116. doi: 10.1016/S0378-8741(01)00265-3. [DOI] [PubMed] [Google Scholar]
  • 15.Dusserre N, Lessard C, Paquette N, et al. Encapsulation of foscarnet in liposomes modifies drug intracellular accumulation, in vitro anti-HIV-1 activity, tissue distribution and pharmacokinetics. AIDS. 1995;9:833–841. doi: 10.1097/00002030-199508000-00002. [DOI] [PubMed] [Google Scholar]
  • 16.Uslu B, Ozkan SA. Determination of lamivudine and zidovudine in binary mixtures using first derivative spectrophotometric, first derivative of the ratio-spectra and high performance liquid chromatography-UV methods. Anal Chim Acta. 2002;466:175–185. doi: 10.1016/S0003-2670(02)00545-7. [DOI] [Google Scholar]
  • 17.Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J Control Release. 2005;106:99–110. doi: 10.1016/j.jconrel.2005.04.007. [DOI] [PubMed] [Google Scholar]
  • 18.Lasic D, Weiner N, Riaz M, Martin F. Liposomes. In: Lieberman A, Rieger M, Banker G, editors. Pharmaceutical Dosage Forms: Disperse Systems. vol. 3. New York, NY: Marcel Dekker; 1998. pp. 43–86. [Google Scholar]
  • 19.Dayan N, Touitou E. Carriers for skin delivery of trihexyphenidyl HCl: ethosomes Vs liposomes. Biomaterials. 2000;21:1879–1885. doi: 10.1016/S0142-9612(00)00063-6. [DOI] [PubMed] [Google Scholar]
  • 20.Van den Bergh BAI, Swartzendruber DC, Bos-Van der Geest A, et al. Development of an optimal protocol for the ultrastructural examination of skin by transmission electron microscopy. J Microscopy. 1997;187:125–133. doi: 10.1046/j.1365-2818.1997.2200779.x. [DOI] [PubMed] [Google Scholar]
  • 21.Kim YH, Ghanem AH, Mahmoud H, Higuchi WI. Short chain alkanols as transport enhancers for lipophilic and polar/ionic permeants in hairless mouse skin: mechanism(s) of action. Int J Pharm. 1992;80:17–31. doi: 10.1016/0378-5173(92)90258-4. [DOI] [Google Scholar]
  • 22.Krishnaiah YSR, Bhaskar P, Satyanarayana V. Penetration-enhancing effect of ethanol water solvent system and ethanolic solution of carvone on transdermal permeability of nimodipine from HPMC gel across rat abdominal skin. Pharm Dev Technol. 2004;9:63–74. doi: 10.1081/PDT-120027419. [DOI] [PubMed] [Google Scholar]
  • 23.Godin B, Touitou E. Mechanism of bacitracin permeation enhancement through the skin and cellular membrane from an ethosomal carrier. J Control Release. 2004;187:1–15. doi: 10.1016/j.jconrel.2003.10.014. [DOI] [PubMed] [Google Scholar]
  • 24.Oussoren C, Magnani M, Fraternale A, et al. Liposomes as carrier of the antiviral agent dideoxycytidine-5′-triphosphate. Int J Pharm. 1999;180:261–270. doi: 10.1016/S0378-5173(99)00016-2. [DOI] [PubMed] [Google Scholar]
  • 25.Brown MS, Goldstein JL. Lipoprotein metabolism in the macrophage: implication for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52:223–261. doi: 10.1146/annurev.bi.52.070183.001255. [DOI] [PubMed] [Google Scholar]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists

RESOURCES