Abstract
A novel niosome formulation is proposed for topical drug delivery of ammonium glycyrrhizinate, a natural compound with an efficacious anti-inflammatory activity. Niosomes were made up of a new non ionic surfactant, α,ω-hexadecyl-bis-(1-aza-18-crown-6) (Bola-surfactant)-Span 80-cholesterol (2:3:1 molar ratio). Niosome vesicles were prepared with the thin layer evaporation method and were physico-chemically characterized. The tolerability of Bola-surfactant both as free molecules or assembled ion niosome vesicles was evaluated in vitro on cultured of human keratinocyte cells (NCTC2544). Human tolerability was evaluated on volunteers. The ability of Bola-niosomes to promote intracellular delivery was evaluated by confocal laser scanning microscopy (CLSM) studies. Human stratum corneum and epidermis (SCE) membranes were used in vitro to investigate the percutaneous permeation. The anti-inflammatory activity of ammonium glycyrrhizinate was evaluated in vivo on human volunteers with a chemically induced erythema. Experimental data show that Bola-niosomes are characterized by a mean size of ∼400 nm and are able to provide an encapsulation efficiency of 40% with respect to the drug amount used during preparation. CLSM showed that Bola-niosomes were able to promote the intracellular uptake of the delivered substances. Bola-niosomes were also able to significantly improve (p <0.001) the percutaneous permeation of ammonium glycyrrhizinate with respect to both the aqueous drug solution and a physical mixture between unloaded Bola-niosomes and the aqueous drug solution. Bola-niosomes showed a suitable tolerability both in vitro and in vivo. Ammonium glycyrrhizinate-loaded Bola-niosomes determined a significant (p <0.001) and noticeable improvement of the in vivo anti-inflammatory activity of the drug. An effective example of conjugating innovative colloidal carriers, coming from pharmaceutical nanotechnology, and therapeutically effective natural compounds, coming from traditional medicine, was reported.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
I.A. Alsarra, A.A. Bosela, S.M. Ahmed, and G.M. Mahrous, Eur. J. Pharm. Biopharm. 59, 485 (2005).
P. Arunothayanun, M.S. Bernard, D.Q. Craig, I.F. Uchegbu, and A.T. Florence, Int. J. Pharm. 201, 7 (2000).
A. Balasubramaniam, V.A. Kumar, and K.S. Pillai, Drug Dev. Ind. Pharm. 28, 1181 (2002).
L.A. Baltina, Curr. Med. Chem. 10, 155 (2003).
B.W. Barry, Eur. J. Pharm. Sci. 14, 101 (2001).
A. Blume, M. Jansen, M. Ghyczy, and J. Gareis, Int. J. Pharm. 99, 219 (1993).
E. Caponetti, D. Chillura-Martino, C. La Mesa, R. Muzzalupo, and L. Pedone, J. Phys. Chem. B 108, 1214 (2004).
G. Cevc and G. Blume, Biochim. Biophys. Acta 1514, 191 (2001).
G. Cevc and D. Gebauer, Biophys. J. 84, 1010 (2003).
M.J. Choi and H.I. Maibach, Skin Pharmacol. Physiol. 18, 209 (2005).
H.M. Courrier, M.P. Krafft, N. Butz, C. Porte, N. Frossard, A. Remy-Kristensen, Y. Mely, F. Pons, and T.F. Vandamme, Biomaterials 24, 689 (2003).
A.A. Date, B. Naik, and M.S. Nagarsenker, Skin Pharmacol. Physiol. 19, 2 (2006).
N. Dayan and E. Touitou, Biomaterials 21, 1879 (2000).
P.K. Eggers, T.M. Fyles, K.D. Mitchell, and T. Sutherland, J. Org. Chem. 68, 1050 (2003).
G.M.M. El Maghraby, A.C. Williams, and B.W. Barry, Int. J. Pharm. 276, 143 (2004).
G.M.M. El Maghraby, A.C. Williams, and B.W. Barry, Int. J. Pharm. 196, 63 (2000).
J.Y. Fang, C.T. Hong, W.T. Chiu, and Y.Y. Wang, Int. J. Pharm. 219, 61 (2001).
Z. Fiume, Int. J. Toxicol. 20, 21 (2001).
M. Fresta, S. Guccione, A.R. Beccari, P.M. Furneri, and G. Puglisi, Bioorg. Med. Chem. 10, 3871 (2002).
M. Fresta, M. Ricci, C. Rossi, P.M. Furieri, and G. Pugliesi, J. Coll Interf Sci. 226, 222 (2000).
C. Fruijtier-Polloth, Toxicology 214, 1 (2005).
P.M. Furneri, M. Fresta, G. Pugliesi, and G. Tempera, Antimicrob. Agents Chemother. 44, 2458 (2000).
B. Godin and E. Touitou, J. Control. Rel. 94, 365 (2004).
R.P. Gude, M.G. Jadhav, S.G. Rao, and A.G. Jagtap, Cancer Biother. Radiopharm. 17, 183 (2002).
S. Jain, P. Singh, V. Mishra, and S.P. Vyas, Immunol. Lett. 101, 41 (2005).
A.M. Kligman and E. Christophers, Arch. Dermatol. 88, 702 (1963).
R.S. Lanigan and T.A. Yamarik, Int. J. Toxicol. 21, 93 (2002).
J.K. Lee, D.B. Kim, J.I. Kim, and P.Y. Kim, Toxicol. In Vitro 14, 345 (2000).
M. Manconi, C. Sinico, D. Valenti, F. Lai, and A.M. Fadda, Int. J. Pharm. 311, 11 (2006).
M. Manconi, C. Sinico, D. Valenti, G. Loy, and A.M. Fadda, Int. J. Pharm. 234, 237 (2002).
M. Manconi, D. Valenti, C. Sinico, F. Lai, G. Loy, and A.M. Fadda, Int. J. Pharm. 260, 261 (2003).
S. Matsui, H. Matsumoto, Y. Sonoda, K. Ando, E. Aizu-Yokota, T. Sato, and T. Kasahara, Int. Immunopharmacol. 4, 1633 (2004).
D.C. McKenzie, C.A. Bunton, D.F. Nicoli, and G. Savelli, J. Phys. Chem. 91, 5709 (1987).
R. Muzzalupo, G. Gente, C. La Mesa, E. Caponetti, D. Chillura-Martino, L. Pedone, and M.L. Saladino, Langmuir 22, 6001 (2006).
R. Muzzalupo, G.A. Ranieri, and C. La Mesa, Langmuir 12, 3157 (1996).
R. Muzzalupo, S. Trombino, F. Iemma, F. Puoci, C. La Mesa, and N. Picci, Colloid Surf. B: Biointerfaces 46, 78 (2005).
D. Paolino, G. Lucania, D. Mardente, F. Alhaique, and M. Fresta, J. Control. Rel. 106, 99 (2005).
L. Sanchez, M. Mitjans, M.R. Infante, and M.P. Vinardell, Pharm. Res. 21, 1637 (2004).
L. Sanchez, M. Mitjans, M.R. Infante, and M.P. Vinardell, Toxicol. Lett. 161, 53 (2006).
H. Schreier and J. Bouwstra, J. Control. Rel. 30, 1 (1994).
A. Shahiwala and A. Misra, J. Pharm. Sci. 5, 220 (2002).
S.I. Simoes, J.M. Tapadas, C.M. Marques, M.E. Cruz, M.B. Martins, and G. Cevc, Eur. J. Pharm. Sci. 26, 307 (2005).
E. Touitou, N. Dayan, L. Bergelson, B. Godin, and M. Eliaz, J. Control. Rel. 65, 403 (2000).
I. Tsujino, T. Yamazaki, M. Masutani, U. Sawada, and T. Horie, Cancer Chemother. Pharmacol. 43, 29 (1999).
I.F. Uchegbu and S.P. Vyas, Int. J. Pharm. 172, 33 (1998).
M.E. Van Kuijk-Meuwissen, L. Mougin, H.E. Junginger, and J.A. Bouwstra, J. Control. Rel. 56, 189 (1998).
B. Vora, A.J. Khopade, and N.K. Jain, J. Control. Rel. 54, 149 (1998).
W.J. Xia and H. Onyuksel, Pharm. Res. 17, 612 (2000).
Z. Zhong, J. Feijen, M.C. Lok, W.E. Hennink, L.V. Christensen, J.W. Yockman, Y.H. Kim, and S.W. Kim, Biomacromol. 6, 3440 (2005).
Acknowledgments
The authors would like to thank Maria Grazia Calvagno Ph.D. (Department of Pharmacobiological Sciences, University of Catanzaro) for her excellent and valuable support in the in vitro experiments (particularly concerning CLSM experiments) and for her helpful discussion and suggestions throughout this paper. The authors also thank Dr. Antony Bridgewood for his revision of the language of this paper. This research was partially supported by the Faculty of Pharmacy of the University “Magna Græcia” of Catanzaro. The authors acknowledge the financial support (PRIN 2005) from MIUR.
Author information
Authors and Affiliations
Corresponding author
Additional information
Part of this research was presented at the 33rd Annual Meeting of the Controlled Release Society in Vienna, Austria, July 22–26, 2006.
Rights and permissions
About this article
Cite this article
Paolino, D., Muzzalupo, R., Ricciardi, A. et al. In vitro and in vivo evaluation of Bola-surfactant containing niosomes for transdermal delivery. Biomed Microdevices 9, 421–433 (2007). https://doi.org/10.1007/s10544-007-9046-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10544-007-9046-6