Mechanisms of a phosphorothioate oligonucleotide delivery by skin electroporation

“…The highly ordered structure of lipid bilayers confers upon the SC an impermeable character. Different techniques, such as iontophoresis (6)(7)(8), electroporation (9,10), chemical enhancers (11), and microprojections (12) have been used to enhance transdermal and topical delivery of antisense oligonucleotides.…”

Section: Introductionmentioning

confidence: 99%

Topical Delivery of Anti-sense Oligonucleotides Using Low-Frequency Sonophoresis

et al. 2004

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“…It was reported that phosphorothioate oligonucleotides seem to interact with some molecular species of the stratum corneum (eg intracellular keratin). 24 Therefore, this nature may decrease the penetration of the AS6 into epidermis and upper dermis; nevertheless, it may be believed that the AS6 concentration is enough to inhibit IL-10 production. On the other hand, only low radioactivity was observed in the anodal gel, the skin under it, and other tissues (blood, liver, spleen, and kidney).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, approximately 6 nmol of AS6 was topically transferred in the skin (2.5 cm 2 ) under the cathodal gel following iontophoresis, and more than 80% of this was intact after 48 h (Figure 2c). As calculated from tissue volume (65 ml/ cm 2 for the viable skin tissue 24 ), the concentration of intact AS6 within the skin was about 29.5 mM (20 nmol Â 30% Â 80%/65 ml Â 2.5 cm 2 ), including AS6 trapped in stratum corneum. This concentration might be enough to have an inhibitory effect on IL-10 production in the skin.…”

Section: Antisense Oligonucleotides For Il-10 Alleviate Dermatitis T mentioning

confidence: 99%

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

et al. 2004

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IL-10 is overexpressed in skin lesions of atopic dermatitis (AD) patients and believed to be an important factor in the pathogenesis of the disease. Thus the regulation of IL-10 production is a potential solution for immunotherapeutic intervention in AD. We examined the topical delivery of an antisense oligonucleotide for mouse IL-10 (AS6) and the therapeutic effect on the skin lesions of NC/Nga mice, a human AD model. Using an iontophoresis system, about 30% of the applied dose of AS6 penetrated the skin and was distributed in the epidermis and upper dermis. Topically delivered AS6 decreased the levels of mRNA and protein of IL-10 in the lesions of NC/Nga mice, with no effect on IL-4 levels. The dorsal lesions of NC/Nga mice disappeared with repeated topical application of AS6. Topically delivered AS6 showed an inhibitory effect on the production of IL-10 in the skin lesions of NC/Nga mice and had a therapeutic effect on the established dermatitis.

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“…Different molecules with the above mechanisms, including monoclonal antibodies (Adams and Weiner 2005), aptamers (Levy-Nissenbaum et al 2008), short peptides (Brown 2010), and other small molecules (Sudimack and Lee 2000), have been proposed for different purposes, such as localization and transportation (nanocarrier/ drug carrier). Passive mechanisms are also involved with the topical application of drugs and their delivery to cells, and oligonucleotides/aptamers have also shown to be involved in the passive mechanism (Regnier et al 1999). Currently, two antibody-conjugated drugs have been approved by the Food and Drug Administration (FDA) to treat cancers, and one of those is in clinical use.…”

Section: Aptamers As Cell Surface Targeting and Intracellular Delivermentioning

confidence: 99%

Cell-targeting aptamers act as intracellular delivery vehicles

Gopinath

Lakshmipriya

Chen

et al. 2016

Appl Microbiol Biotechnol

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Aptamers are single-stranded nucleic acids or peptides identified from a randomized combinatorial library through specific interaction with the target of interest. Targets can be of any size, from small molecules to whole cells, attesting to the versatility of aptamers for binding a wide range of targets. Aptamers show drug properties that are analogous to antibodies, with high specificity and affinity to their target molecules. Aptamers can penetrate disease-causing microbial and mammalian cells. Generated aptamers that target surface biomarkers act as cell-targeting agents and intracellular delivery vehicles. Within this context, the "cell-internalizing aptamers" are widely investigated via the process of cell uptake with selective binding during in vivo systematic evolution of ligands by exponential enrichment (SELEX) or by cell-internalization SELEX, which targets cell surface antigens to be receptors. These internalizing aptamers are highly preferable for the localization and functional analyses of multiple targets. In this overview, we discuss the ways by which internalizing aptamers are generated and their successful applications. Furthermore, theranostic approaches featuring cell-internalized aptamers are discussed with the purpose of analyzing and diagnosing disease-causing pathogens.

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Mechanisms of a phosphorothioate oligonucleotide delivery by skin electroporation

Cited by 52 publications

References 33 publications

Topical Delivery of Anti-sense Oligonucleotides Using Low-Frequency Sonophoresis

Topical Delivery of Anti-sense Oligonucleotides Using Low-Frequency Sonophoresis

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

Cell-targeting aptamers act as intracellular delivery vehicles

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