Topical Delivery of Thymidine Dinucleotide to Induce p53 Generation in the Skin by Elastic Liposome

Authors: Yi-Ping Fang, Yi-Ting Wong

Abstract:

Transcription factor p53 has a powerful tumor suppressing function that is associated with many cancers. However, p53 of the molecular weight was higher make the limitation across to skin or cell membrane. Thymidine dinucleotide (pTT), an oligonucleotide, can activate the p53 transcription factor. pTT is a hydrophilic and negative charge oligonucleotide, which delivery in to cell membrane need an appropriate carrier. The aim of this study was to improve the bioavailability of the nucleotide fragment, thymidine dinucleotide (pTT), using elasic liposome carriers to deliver the drug into the skin. The study demonstrate that dioleoylphosphocholine (DOPC) incorporated with sodium cholate at molar ratio 1:1 can archived the particle size about 220 nm. This elastic liposome could penetration through skin from stratum corneum to whole epidermis by confocal laser scanning microscopy (CLSM). Moreover, we observed the the slight increase in generation of p53 by western blot.

Keywords: Elastic liposome, Tymidine dinucleotide, p53, Topical delivery

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1326706

References:

[1] N. F. Box, T. Terzian, "The role of p53 in pigmentation, tanning and melanoma," Pigment Cell Melanoma Res, vol. 21, pp. 525-533, Oct 2008.
[2] A. Sigal, V. Rotter, "Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome. Cancer Res," Cancer Res, vol. 60, pp. 6788-6793, Dec 2000.
[3] M. Oren, A. Damalas, T. Gottlieb, D. Michael, J. Taplick, J. F. Leal, R. Maya, M. Moas, R. Seger, Y. Taya, A. Ben-Ze'Ev, "Regulation of p53: intricate loops and delicate balances," Ann. N. Y. Acad. Sci., vol. 973. pp. 374-383, Nov 2002.
[4] P. M. Rodust, E. Stockfleth, C. Ulrich, M. Leverkus, J. Eberle, "UV-induced squamous cell carcinoma - a role for antiapoptotic signalling pathways," Br. J. Dermatol. vol. 161 Suppl 3, pp. S107-S115, Nov 2009.
[5] C. L. Benjamin, S. E. Ullrich, M. L. Kripke, H. N. "p53 tumor suppressor gene: a critical molecular target for UV induction and prevention of skin cancer," Photochem. Photobiol., vol. 84. pp. 55-62, Jan-Feb 2008.
[6] D. A. Goukassian, M. S. Eller, M. Yaar, B. A. Gilchrest, "Thymidine dinucleotide mimics the effect of solar simulated irradiation on p53 and p53-regulated proteins," J. Invest. Dermatol., vol. 112. pp. 25-31, Jan 1999.
[7] E. Fattal, G. Barratt, "Nanotechnologies and controlled release systems for the delivery of antisense oligonucleotides and small interfering RNA," Br. J. Pharmacol., vol. 157. pp. 179-194, May 2009.
[8] R. Parhi, S. Mondal, P. M. Kumar, "Novel Penetration Enhan cers for Skin Applications: A Review," Curr. Drug. Deliv., Oct 2011. In press.
[9] D. Papakostas, F. Rancan, W. Sterry, U. Blume-Peytavi, A. Vogt, "Nanoparticles in dermatology," Arch. Dermatol. Res., vol. 308. pp. 533-550, Oct 2011.
[10] L. Li, Y. Zhang, S. Han, Z. Qu, J. Zhao, Y. Chen, Z. Chen, J. Duan, Y. Pan, X. Tang, "Penetration enhancement of lidocaine hydrochlorid by a novel chitosan coated elastic liposome for transdermal drug delivery," J. Biomed. Nanotechnol., vol. 7. pp. 704-713, Oct 2011.
[11] G. Cevc, G. Blume, "Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force," Biochim. Biophys. Acta, vol. 1104. pp. 226-232, Feb 1992.
[12] G. Cevc, G.Blume, "New, highly efficient formulation of diclofenac for the topical, transdermal administration in ultradeform drug carriers, Transfersomes," Biochim. Biophys. Acta, vol. 1514. pp. 191-205, Oct 2001.
[13] H. A. Benson, "Elastic liposomes for topical and transdermal drug delivery," Curr Drug Deliv. vol. 6. pp. 217-226, Jul 2009.
[14] S. Duangjit, P. Opanasopit, T. Rojanarata, T. Ngawhirunpat, "Effect of Edge Activator on Characteristic and in Vitro Skin Permeation of Meloxicam Loaded in Elastic Liposomes," Adv. Mat. Res., vol. 194 pp. 537-540, Feb 2011.
[15] C. D. Pirvu, C. Hlevca, A. Ortan, R. Prisada, "Elastic vesicles as drugs carriers through the skin," Farmacia, vol. 58 pp.128-135, 2010.
[16] D. A. Goukassian, M. S. Eller, M. Yaar, B. A. Gilchrest, "Thymidine dinucleotide mimics the effect of solar simulated irradiation on p53 and p53-regulated proteins," J. Invest. Dermatol., vol. 112 pp. 25-31, Jan 1999.
[17] P. L. Honeywell-Nguyen, J. A. Bouwstra, "The in vitro transport of pergolide from surfactant-based elastic vesicles through human skin: a suggested mechanism of action," J. Control. Release, vol. 86. pp. 145-156, Jan 2003.
[18] J. Mönkkönen, A. Urtti, "Lipid fusion in oligonucleotide and gene delivery with cationic lipids," Adv. Drug Deliv. Rev., vol. 34 pp. 37-49, Oct 1998.
[19] D. Hirsch-Lerner, M. Zhang, H. Eliyahu, M. E. Ferrari, C. J. Wheeler, Y. Barenholz, "Effect of "helper lipid" on lipoplex electrostatics," Biochim. Biophys. Acta, vol. 1714. pp. 71-84, Aug 2005.
[20] G. Cevc, "Transfersomes, liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration, and transdermal drug delivery," Crit. Rev. Ther. Drug Carrier Syst., vol. 13. pp. 257-388, 1996.
[21] G. Cevc, G. Blume, A. Schätzlein, D. Gebauer, A. Paul, "The skin: a pathway for systemic treatment with patches and lipid-based agent carriers," Adv. Drug Deliv. Rev, vol. 18. pp. 349-378, Feb 1996.
[22] G. Cevc, A. Schätzlein, H. Richardsen, U. Vierl "Overcoming semi-permeable barriers, such as the skin, with ultradeformable mixed lipid vesicles, Transfersomes, liposomes or mixed lipid micelles". Langmuir, vol. 19. pp. 10753-10763, Aug 2003.
[23] Y. P. Fang, "Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier," Int. J. Nanomedicine, vol. 6. pp. 3373-3381, Dec 2011.