Abstract
The aim of this study was to investigate the lipophilic prodrug as a means of promoting acyclovir (ACV) that exhibited biphasic insolubility into the ethosomes for optimum skin delivery. Acyclovir Palmitate (ACV-C16) was synthesized as the lipophilic prodrug of ACV. The ethosomal system and the liposomal system bearing ACV or ACV-C16 were prepared, respectively. The systems were characterized for shape, zeta potential value, particle size, and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy were used for the percutaneous absorption studies. The results showed that the entrapment efficiency of ACV-C16 ethosomes (87.75%) were much higher than that of ACV ethosomes (39.13%). The quantity of drug in the skin from ACV-C16 ethosomes at the end of the 24 h transdermal experiment (622.89 μg/cm2) was 5.30 and 3.43 times higher than that from ACV-C16 hydroalcoholic solution and ACV ethosomes, respectively. This study indicated that the binary combination of the lipophilic prodrug ACV-C16 and the ethosomes synergistically enhanced ACV absorption into the skin.
Similar content being viewed by others
References
Arora, A., Prausnitz, M., and Mitragotri, S., Micro-scale devices for transdermal drug delivery. Int. J. Pharm., 364, 227–236 (2007).
Cai, Q. -S., Feng, M. -Q., and Huang, H., High yield synthesis, structure confirm of acyclovir palmitate and its role in inhibiting hepatitics in vivo. J. Med. Sci., 34, 486–490 (2007).
Dayan, N. and Touitou, E., Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes. Biomaterials, 21, 1879–1885 (2000).
Degim, I. -T., New tools and approaches for predicting skin permeability. Drug Discov Today, 11, 517–523 (2006).
Denet, A. -R. and Préat, V., Transdermal delivery of timolol by electroporation through human skin. J. Control. Release, 88, 253–262 (2003).
Dubey, V., Mishra, D., and Jain, N. -K., Melatonin loaded ethanolic liposomes: Physicochemical characterization and enhanced transdermal delivery. Eur. J. Pharm. Biopharm., 67, 398–405 (2007).
Elsayed, M. -M., Abdallah, O. -Y., Naggar, V. -F., and Khalafallah, N. -M, Deformable liposomes and ethosomes: Mechanism of enhanced skin delivery. Int. J. Pharm., 322, 60–66 (2006).
Elsayed, M. -M., Abdallah, O., and Y., Naggar, V. -F., and Khalafallah, N. -M., Lipid vesicles for skin delivery of drugs: Reviewing three decades of research. Int. J. Pharm., 332, 1–16 (2007).
Feng, M., Cai, Q., Huang, H., and Zhou, P., Liver targeting and anti-HBV activity of reconstituted HDL-acyclovir palmitate complex. Eur. J. Pharm. Biopharm., 68, 688–693 (2008).
Fry, D. -W., White, J. -C., and Goldman, I. -D., Rapid separation of low molecular weight solutes from liposomes without dilution. J. Anal. Biochem., 90, 809–815 (1978).
Gulati, M., Grover, M., and Singh, S., Lipophilic drug derivatives in liposomes. J. Int. J. Pharm., 165, 129–168 (1998).
Horwitz, E., Pisanty, S., Czerninski, R., Helser, M., Eliav, E., and Touitou, E., A clinical evaluation of a novel liposomal carrier for acyclovir in the topical treatment of recurrent herpes labialis. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 87, 700–705 (1999).
Jain, S., Tiwary, A. -K., Sapra, B., and Jain, N. -K., Formulation and evaluation of ethosomes for transdermal delivery of lamivudine. AAPS Pharm. Sci. Tech., 8, E1–E9 (2007).
Law, S. -L. and Hung, H. -Y., Properties of acyclovir-containing liposomes for potential ocular delivery. Int. J. Pharm., 161, 253–259 (1998).
Liu, H., Tang, R., He, X. -X., and Zhang, Y., Effects of liposomes formulation and preparation method on the stability of acyclovir palmitate liposomes. Yao Xue Xue Bao, 37, 563–566 (2002).
Maestrelli, F., Capasso, G., Gonzalez-Rodriguez, M. -L., Rabasco, A. -M., Ghelardini, C., and Mura, P., Effect of preparation technique on the properties and in vivo efficacy of benzocaine-loaded ethosomes. J. Liposome Res., 4, 1–8 (2009).
Naik, A., Kalia, Y. -N., and Guy, R., Transdermal drug delivery: overcoming the skin’s barrier function. Pharm. Sci. Technol. Today, 3, 318–326 (2000).
Padula, C., Sartori, F., Marra, F., and Santi, P., The influence of iontophoresis on acyclovir transport and accumulation in rabbit ear skin. Pharm. Res., 22, 1519–1524 (2005).
Paolino, D., Lucania, G., Mardente, D., Alhaique, F., and 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, 106, 99–110 (2005).
Paveliæ, Z., Skalko, B. -N., Filipoviæ, G. -J., Martinac, A., and Jalsenjak, I., Development and in vitro evaluation of a liposomal vaginal delivery system for acyclovir. J. Control. Release, 106, 34–43 (2005).
Prausnitz, M. -R., A practical assessment of transdermal drug delivery by skin electroporation. Adv. Drug Deliv. Rev., 35, 61–76 (1999).
Sorensen, E. -N., Weisman, G., and Vidaver, G. -A., A Sephadex column for measuring uptake and loss of low molecular weight solutes from small vesicles. Anal. Biochem, 82, 376–384 (1977).
Touitou, E., Dayan, N., Bergelson, L., Godin, B., and Eliaz, M., Ethosomes-novel vesicular carriers for enhanced delivery: Characterization and skin penetration properties. J. Control. Release, 65, 403–418 (2000a).
Touitou, E., Godin, B., and Weiss, C., Enhanced delivery of drugs into and across the skin by ethosomal carriers. Drug Dev. Res., 50, 406–415 (2000b).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhou, Y., Wei, YH., Zhang, GQ. et al. Synergistic penetration of ethosomes and lipophilic prodrug on the transdermal delivery of acyclovir. Arch. Pharm. Res. 33, 567–574 (2010). https://doi.org/10.1007/s12272-010-0411-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-010-0411-2