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A controllable transdermal drug delivery preparation based on framework nucleic acid and its preparation method

A drug delivery and nucleic acid technology, which can be applied to pharmaceutical formulations, medical preparations with inactive ingredients, and medical preparations containing active ingredients, etc. Uncontrollable depth and other problems, to achieve the effect of solving the uncontrollable shape, size and penetration depth and good stability

Active Publication Date: 2021-12-03
SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The present invention provides a controllable transdermal drug delivery preparation based on framework nucleic acid and its preparation method to solve the problem of rapid decomposition and digestion of framework nucleic acid caused by invasive needle injection to realize the in vivo transportation of framework nucleic acid, resulting in the target The problem of low bioavailability of the site
In addition, it also solves the problem of uncontrollable shape, size and transdermal depth of transdermal preparations in the prior art, and provides a new way for transdermal drug delivery

Method used

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  • A controllable transdermal drug delivery preparation based on framework nucleic acid and its preparation method
  • A controllable transdermal drug delivery preparation based on framework nucleic acid and its preparation method
  • A controllable transdermal drug delivery preparation based on framework nucleic acid and its preparation method

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Embodiment 1: Preparation of framework nucleic acid

[0047] Provide framework nucleic acid: DNA single strands are dissolved in a buffer solution for assembly. Specifically, DNA single strands are mixed in a certain proportion, and Mg-containing 2+ In the synthesis buffer, mix well, anneal, self-assemble to form framework nucleic acid.

[0048] Framework nucleic acid fluorescent labeling: obtained by extending the DNA single strand at the corresponding position and incubating with the complementary DNA single strand of the modified fluorescent molecule at room temperature for hybridization.

[0049] In this embodiment, eight kinds of framework nucleic acids with different structures, sizes and dimensions are provided, as shown in Table 1.

[0050] Table 1 Eight framework nucleic acids and their corresponding fluorescent labels

[0051]

Embodiment 2

[0052] Example 2: Verification of the morphology and size of the framework nucleic acid

[0053] (1) Dimensional measurement of the structure

[0054] The hydrodynamic diameter (Dh) was measured with a particle size analyzer Zetasizernano Z (Malvern), and the measurement was repeated at least three times. The result is as figure 1 As shown, the measured tetrahedral nanostructures: the average hydrodynamic diameters (Dh) of TH21, TH37 and TH337 are ~ (approximately, the same below) 17nm, ~44nm and ~187nm (theoretical sizes are respectively: ~7nm , ~12nm, ~100nm). Two six-helix rod-like nanostructures: 6H714 and 6H14498 have two peaks, corresponding to width ~ 30nm and rod length ~ 66 / 220nm (theoretical dimensions are: width ~ 6nm, rod length ~ 20nm / 400nm). The remaining larger rectangular or triangular nanostructures: R13730, B14498 and T14498 have similar average Dh, between 140-170nm (theoretical dimensions are: ~70×100nm, ~6×40×60nm, ~120nm side length).

[0055] (2) Ele...

Embodiment 3

[0057] Example 3: Observation of cellular uptake behavior of framework nucleic acids

[0058] (1) Cell culture and cell viability detection:

[0059] Normal dermal fibroblasts (normal dermal fibroblast or NDF) (purchased from CellResearch Corporation Pte Ltd, Singapore) and immortalized keratinocytes HaCaT (purchased from American Type Culture Collection, ATCC) were cultured in 10% fetal bovine serum (PBS), 1% gelatin serine (PS), 4mM L-glutamine (L-glutamine) in the DMEM medium (4500mg / L), 37 ℃, 5% CO 2 , cultured in saturated humidity, adding fresh medium every 2-3 days.

[0060] Alamarblue reagent was added to the medium at a volume ratio of 1:100, and after incubation for 8 hours, fluorescence measurement (570 / 585nm) was performed to detect cell viability.

[0061] (2) To study the influence of incubation time on the cellular uptake behavior of TH21 DNA tetrahedral nanostructures:

[0062] Fluorescence-labeled TH21 was added to normal skin fibroblasts at a final concent...

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Abstract

The present invention relates to a controllable transdermal drug delivery preparation based on framework nucleic acid, the controllable transdermal drug delivery preparation includes a DNA drug complex, the DNA drug complex is a frame nucleic acid and a drug molecule linked together, the Drug molecules are transdermally administrable drugs. The present invention also relates to a method for preparing a controllable transdermal drug delivery preparation based on framework nucleic acid, which includes providing framework nucleic acid, and the framework nucleic acid is coupled with drug molecules to form a DNA drug complex. The present invention avoids the problem of low bioavailability of the target site due to rapid decomposition and digestion of the framework nucleic acid caused by the delivery route of the framework nucleic acid in vivo through invasive needle injection. The present invention solves the problem of uncontrollable shape, size and transdermal depth of transdermal preparations in the prior art by precisely controlling the shape and size of the framework nucleic acid, and provides a new way for transdermal drug delivery.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a framework nucleic acid-based controllable transdermal drug delivery preparation and a preparation method thereof. Background technique [0002] Transdermal drug delivery (TDD) refers to a drug delivery method in which drugs are coated or applied on the skin surface. Compared with traditional oral and injection administration methods, transdermal administration has the following advantages: ① After the drug is transdermally absorbed, it can maintain a stable blood drug concentration for a long time, avoiding the peak and valley of drug concentration in traditional administration ②The drug bypasses the gastrointestinal tract or liver to directly metabolize, avoiding gastrointestinal tract stimulation and liver first-pass effect; ③Patients can take the drug independently or stop the drug at any time, which reduces the pain of injection medication and improves the patient ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K47/26A61K9/00A61K9/70A61K31/704A61P35/00
CPCA61K9/0014A61K9/7023A61K31/704A61K47/26A61K47/549A61P35/00
Inventor 樊春海徐臣杰克里斯蒂安·维拉亚王丽华李茜谢茉
Owner SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI