Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier

Yi-Ping FangDepartment of Biotechnology, Yuanpei University, Hsinchu, TaiwanIntroduction: Transcription factor p53 has a powerful tumor suppressing function that is associated with many cancers. Since the molecular weight of p53 is 53 kDa, it is difficult to transport across cell membranes. Thymidin...

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Autor principal:	Fang YP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a0e66ab29be94501af168e2f34ef4073
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spelling	oai:doaj.org-article:a0e66ab29be94501af168e2f34ef40732021-12-02T03:01:54ZTopical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier1176-91141178-2013https://doaj.org/article/a0e66ab29be94501af168e2f34ef40732011-12-01T00:00:00Zhttp://www.dovepress.com/topical-delivery-of-dna-oligonucleotide-to-induce-p53-generation-in-th-a8919https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yi-Ping FangDepartment of Biotechnology, Yuanpei University, Hsinchu, TaiwanIntroduction: Transcription factor p53 has a powerful tumor suppressing function that is associated with many cancers. Since the molecular weight of p53 is 53 kDa, it is difficult to transport across cell membranes. Thymidine dinucleotide (pTT) is an oligonucleotide that can activate the p53 transcription factor and trigger the signal transduction cascade. However, the negative charge and high water solubility of pTT limit its transport through cellular membranes, thereby preventing it from reaching its target in the nucleus. A suitable delivery carrier for pTT is currently not available.Objective: The purpose of this study was to employ a nanoscale liposomal carrier to resolve the delivery problem, and increase the bioavailability and efficiency of pTT.Methodology: The approach was to employ liposomes to deliver pTT and then evaluate the particle size and zeta potential by laser light scattering (LLS), and permeation properties of pTT in vitro in a Franz diffusion assembly, and in vivo in a murine model using confocal laser scanning microscopy (CLSM).Results: We found that dioleoylphosphatidylethanolamine (DOPE) combined with cholesterol 3 sulfate (C3S) were the best ingredients to achieve an average desired vehicle size of 133.6 &plusmn; 2.8 nm, a polydispersity index (PDI, representing the distribution of particle sizes) of 0.437, and a zeta potential of &minus;93.3 &plusmn; 1.88. An in vitro penetration study showed that the liposomal carrier was superior to the free form of pTT at 2&ndash;24 hours. CLSM study observed that the penetration depth of pTT reached the upper epidermis and potential of penetration maintained up to 24 hours.Conclusion: These preliminary data demonstrate that nanosized DOPE/C3S liposomes can be exploited as a potential carrier of drugs for topical use in treating skin diseases.Keywords: thymidine dinucleotide, p53, liposome, permeation ability, confocal laser scanning microscopyFang YPDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 3373-3381 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Fang YP Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier
description	Yi-Ping FangDepartment of Biotechnology, Yuanpei University, Hsinchu, TaiwanIntroduction: Transcription factor p53 has a powerful tumor suppressing function that is associated with many cancers. Since the molecular weight of p53 is 53 kDa, it is difficult to transport across cell membranes. Thymidine dinucleotide (pTT) is an oligonucleotide that can activate the p53 transcription factor and trigger the signal transduction cascade. However, the negative charge and high water solubility of pTT limit its transport through cellular membranes, thereby preventing it from reaching its target in the nucleus. A suitable delivery carrier for pTT is currently not available.Objective: The purpose of this study was to employ a nanoscale liposomal carrier to resolve the delivery problem, and increase the bioavailability and efficiency of pTT.Methodology: The approach was to employ liposomes to deliver pTT and then evaluate the particle size and zeta potential by laser light scattering (LLS), and permeation properties of pTT in vitro in a Franz diffusion assembly, and in vivo in a murine model using confocal laser scanning microscopy (CLSM).Results: We found that dioleoylphosphatidylethanolamine (DOPE) combined with cholesterol 3 sulfate (C3S) were the best ingredients to achieve an average desired vehicle size of 133.6 &plusmn; 2.8 nm, a polydispersity index (PDI, representing the distribution of particle sizes) of 0.437, and a zeta potential of &minus;93.3 &plusmn; 1.88. An in vitro penetration study showed that the liposomal carrier was superior to the free form of pTT at 2&ndash;24 hours. CLSM study observed that the penetration depth of pTT reached the upper epidermis and potential of penetration maintained up to 24 hours.Conclusion: These preliminary data demonstrate that nanosized DOPE/C3S liposomes can be exploited as a potential carrier of drugs for topical use in treating skin diseases.Keywords: thymidine dinucleotide, p53, liposome, permeation ability, confocal laser scanning microscopy
format	article
author	Fang YP
author_facet	Fang YP
author_sort	Fang YP
title	Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier
title_short	Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier
title_full	Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier
title_fullStr	Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier
title_full_unstemmed	Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier
title_sort	topical delivery of dna oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (ptt)-encapsulated liposomal carrier
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/a0e66ab29be94501af168e2f34ef4073
work_keys_str_mv	AT fangyp topicaldeliveryofdnaoligonucleotidetoinducep53generationintheskinviathymidinedinucleotidepttencapsulatedliposomalcarrier
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Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier

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