Skin-permeating carrier containing nucleic acid complex and use thereof
A technology of skin penetration and compound, which is applied in the field of skin penetration carrier containing nucleic acid complex and its application, which can solve the problems that the effectiveness and stability of drugs cannot be guaranteed.
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Embodiment 1
[0197] Example 1: Preparation of biologically active nucleic acid, carrier peptide nucleic acid and complex using them.
[0198] To confirm the skin penetration and skin maintenance effects of the nucleic acid complex of structural formula (1) according to the present invention, IFI16, a gene targeting psoriatic disease, was used as a target gene. IFI16 is a protein commonly expressed in the skin of patients with psoriasis and is considered an important target for the treatment of psoriasis (upregulation of interferon-inducible protein 16 leads to psoriasis by modulating chemokine production in keratinocytes Disease 6:25381).
[0199] To evaluate the skin penetration and skin retention of nucleic acid complexes, antisense peptide nucleic acid (PNA) and RNA were used as bioactive nucleic acids against IFI16.
[0200] The biologically active nucleic acids (antisense PNA and RNA) of the present invention have the sequences shown in SEQ ID NO: 1-9. The peptide nucleic acid-based...
Embodiment 2
[0207] Example 2: Analysis of Skin Penetration of Nucleic Acid Complexes Comprising Biologically Active Nucleic Acids and Carrier Peptide Nucleic Acids
[0208] In order to analyze the skin penetration of the complexes prepared in Example 1, a predetermined amount of each compound was applied to the back of nude mice, and then left for 1, 3 and 24 hours, and the tissue of the applied area was biopsied. The biopsied tissues were fixed in 4% formalin solution, kept for 1 day, sectioned into 20 μm sections using a microtome, and mounted on glass slides. The affixed tissue was observed under a fluorescence microscope to check whether the complex penetrated the skin.
[0209] The nucleic acid complexes used in this example are shown in Table 3 below.
[0210] [Table 3] Nucleic acid complexes used for analysis of skin penetration
[0211] name nucleic acid complex single siRNA SEQ ID NO:8 siRNA duplex SEQ ID NO: 8 and 10 Single PNA SEQ ID NO:1 ...
Embodiment 3
[0213] Example 3: Analysis of the skin penetration of a skin permeable carrier comprising a complex having the structure of formula (1) to which a low molecular weight substance is bound via a linker
[0214] In order to analyze the skin penetration of the skin permeable carrier in which the low-molecular-weight substance was bound to each complex via a linker compared with each complex prepared in Example 1, a predetermined amount of each complex was applied to the back of nude mice , followed by leaving it on for 0, 3 and 24 hours, biopsies were taken from the area of application. Biopsies were fixed in 4% formalin, kept for 1 day, sectioned into 20 μm sections using a microtome, and mounted on glass slides. The affixed tissue was observed by fluorescence microscopy to examine the transdermal delivery of the skin-permeable vehicle, in which low molecular weight substances were bound to each nucleic acid complex.
[0215] The nucleic acid complexes used in this example are...
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