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Nano-micelles activated by short-time near-infrared illumination for rapidly releasing medicines

A near-infrared light and nanomicelle technology is applied in the preparation of nanomicelles and the application field of rapid drug release, which can solve the problems of slow drug release rate, thermal damage to cells and tissues, unfavorable clinical application, etc., and achieves short illumination time. , good stability and high drug release efficiency

Active Publication Date: 2021-03-09
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, for Tm 3+ Doped UCNPs, electrons reach high-energy excited states 1 D. 2 The transition of is often difficult to occur, so from 1 D. 2 → 3 h 6 The quantum yield of ultraviolet light emission generated by the transition is very low (usually less than 1%), resulting in a slow release rate of the drug, often requiring several hours of light stimulation to achieve the drug concentration required for treatment, which may cause thermal damage to the tissue. damage, which is not conducive to the further development of clinical application

Method used

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  • Nano-micelles activated by short-time near-infrared illumination for rapidly releasing medicines
  • Nano-micelles activated by short-time near-infrared illumination for rapidly releasing medicines
  • Nano-micelles activated by short-time near-infrared illumination for rapidly releasing medicines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1: Combining image 3 , Synthesis of 800CW modified upconversion nanoparticles UCNPs-CW.

[0021] 200mg NaYF 4 :Gd@NaYF 4 : Er, Yb@NaYF 4 : Yb, Nd(UCNPs) dispersed in 10mL CHCl 3 Add 50mg of alendronic acid (ADA), 6mL of pure water and 4mL of ethanol, and adjust the pH value of the mixture to about 2 with 1M hydrochloric acid. After stirring at room temperature for 30 minutes, the upper aqueous phase was collected, centrifuged to obtain UCNPs-ADA, washed several times with pure water, and dispersed in 10 mL of pure water. Then mix 5mL 1mg / mL UCNPs-ADA with 3μL 0.5mM Mixed and stirred overnight at room temperature, centrifuged and washed several times with THF, dispersed in 5 mL THF (Solution A). After mixing 2 μL octanoic acid with 100 μL EDC (0.1M), 100 μL NHS (0.1M) and 300 μL THF and stirring at room temperature for 2 hours, it was added to 5 mL of solution A and stirred at room temperature for 8 h. The obtained hydrophobic UCNPs-CW were centrifuged, ...

Embodiment 2

[0022] Example 2: Combining Figure 4 , Synthesis of amphiphilic polymer long-chain P-DASA.

[0023] Add 15.48mmol n-dodecylamine and 15.48mmol n-dodecyl isocyanate to 130mL CH 2 Cl 2 , stirred at room temperature for 1 h under nitrogen protection, then added 15.48 mmol of malonyl chloride and heated to reflux for 1 h. After cooling to room temperature, add 60mL of 1M hydrochloric acid and mix well, and the crude product is washed with CH 2 Cl 2 extraction. The organic phase was washed with water and MgSO 4 Drying and purification by column chromatography (hexane: ethyl acetate = 9:1 to 4:1) gave product 1.

[0024] 13.6 mmol of 2-furan aldehyde was added to 27 mL of an aqueous solution containing 13.6 mmol of compound 1, and stirred at room temperature for 10 h. use CH 2 Cl 2 Extraction product (compound 2), organic phase is passed through MgSO 4 Dry, filter and dry in vacuo.

[0025] 2.32 mmol of 6-azido-N-ethylhexan-1-amine was added to 5 mL of a THF solution con...

Embodiment 3

[0027] Example 3: Binding figure 1 , Synthesis of upconversion nanomicelle UCNPs-CW / DOX@P-DASA.

[0028] 2 mg DASA-PEG was dispersed in 2.7 mL THF, mixed with 1 mg UCNPs-CW and 100 μL 0.4 mg / mL DOX and sonicated for 20 min. The mixture was then added dropwise to 60 mL of water and stirred at 37 °C for 8 h. The generated upconversion nanomicelle UCNPs-CW / DOX@P-DASA was collected by centrifugation (4000r, 5 minutes) and dispersed in 2 mL of water.

[0029] Nanomicelle DOX@P-DASA without UCNPs-CW was synthesized using a similar method, and UCNPs-CW was not added during the synthesis.

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Abstract

The invention relates to a preparation method of nano-micelles with a short-time near-infrared illumination response and use of the nano-micelles in rapid medicine release. The method uses an amphiphilic polymer chain P-DASA formed by utilizing hydrophilic polyethylene glycol and a hydrophobic donor receptor Stenhouse adduct (DASA), and the nano-micelles coated with Er <3+> doped up-conversion nanoparticles (UCNPs) and an anti-cancer medicine adriamycin are prepared. Under a near-infrared irradiation, green light (541 nm) emitted by the UCNPs promotes the hydrophobic DASA to be converted intohydrophilicity, micelle disintegration is caused, adriamycin is released, and after a stimulation of the illumination (808 nm, 2 W / cm<2>) for only 5 min, a release rate of the medicine reaches 80% orabove within 30 min. The invention provides a near-infrared light-controlled medicine release system activated by short-time illumination and the near-infrared light-controlled medicine release systemhas important significance in clinical use and development of up-conversion nano materials in the fields of medicine carrying and accurate cancer diagnosis and treatment.

Description

[0001] 1. Technical field [0002] The invention relates to the technical field of application of nano-micelle drug loading system, in particular to a preparation method of nano-micelle responding to short-time near-infrared light and its application in rapid drug release. [0003] 2. Background technology [0004] Polymer nanomaterials with micellar structure have been widely used in biomedical research and disease treatment. They are usually formed by the self-assembly of long chains of amphiphilic polymers in aqueous solution. Inside, the hydrophilic part is exposed to the outside, forming nanoparticles with a hydrophobic inner core and a hydrophilic outer layer that are stably dispersed in aqueous solution. Its hydrophilic shell provides good water solubility and biocompatibility, while the hydrophobic core has good drug loading capacity, so it becomes an ideal drug delivery vehicle. [0005] By modifying stimuli-responsive groups in the long chains of polymers as the stru...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K41/00A61K47/34A61K31/704A61P35/00
CPCA61K9/1075A61K9/0009A61K41/0042A61K47/34A61K31/704A61P35/00
Inventor 鞠熀先刘颖张玥
Owner NANJING UNIV
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