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Dual-functional nanoparticle, soluble microneedle and preparing method and application of nanoparticle

A nanoparticle and dual-function technology, applied in the field of pharmaceutical preparations, can solve the problems of drug dumping and poor biocompatibility, and achieve the effects of increasing encapsulation efficiency, improving targeting, and inhibiting tumor effects

Active Publication Date: 2019-11-15
SUN YAT SEN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the existing research still has the following problems: (1) the photosensitizer or nanocarrier material used is a non-degradable material with poor biocompatibility; (2) the use of simple chemotherapy drugs requires frequent administration to achieve effective tumor treatment (3) The chemotherapy drugs are entrapped in MNs in a free form, and the drugs are released rapidly and in large quantities after the MNs are dissolved, and there is a risk of drug dumping

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  • Dual-functional nanoparticle, soluble microneedle and preparing method and application of nanoparticle
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  • Dual-functional nanoparticle, soluble microneedle and preparing method and application of nanoparticle

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preparation example Construction

[0045] In one embodiment of the present invention, a method for preparing bifunctional nanoparticles is provided, comprising the following steps:

[0046] (1) The oil phase solution is mixed with chemotherapeutic drugs to obtain solution A, and the oil phase solution is a volatile organic solvent solution of polyglycolic acid polylactic acid copolymer PLGA and cationic phospholipid DOTAP;

[0047] (2) Under the conditions of water bath and magnetic stirring, the aqueous phase solution and the photosensitizer solution are mixed to obtain solution B, and the aqueous phase solution is an alcohol solution of vitamin E succinate;

[0048] (3) Slowly drip solution A into solution B, and continue stirring after the addition is completed to form a uniform nanoparticle solution;

[0049] (4) Centrifuge the prepared nanoparticle solution, wash it, and resuspend it in PBS to obtain a monofunctional nanoparticle solution;

[0050] (5) The hyaluronic acid solution is dropped into the prep...

Embodiment 1

[0082] Embodiment 1 Preparation of bifunctional nanoparticles

[0083] PTX (concentration of 0.2 mg / ml in acetone), PLGA (concentration of 3.6 mg / ml in acetone) and DOTAP (concentration of 0.4 mg / ml in acetone) were dissolved in acetone solution as oil phase , the dosage ratio of PLGA:DOTAP is 9:1 (equivalent to 10% of DOTAP in the solution in the oil phase material).

[0084] Dissolve TPGS (concentration 2 mg / ml in ethanol solution) in 4% (w / v) ethanol solution at 65°C in a water bath as the water phase; dissolve ICG (concentration 1 mg / ml in methanol) In 20% (v / v) methanol solution.

[0085] Add 100 μl of the methanol solution of ICG dropwise into the TPGS ethanol solution (2.5 ml) preheated in a water bath at 65° C. under magnetic stirring, and then add 500 μl of the oil phase solution dropwise into the above TPGS ethanol solution , continue to stir for 20 min under the condition of 35°C water bath to form uniform nanoparticles.

[0086]Place the prepared nanoparticle so...

Embodiment 2

[0088] The preparation of embodiment 2 bifunctional nanoparticles

[0089] PTX (0.2mg / ml), PLGA (3.2mg / ml) and DOTAP (0.8mg / ml) are dissolved in acetone solution, as the oil phase, PLGA:DOTAP dosage ratio is 8:2, (equivalent to the oil phase In the material, the content of DOTAP in the solution was 20%).

[0090] TPGS (2mg / ml) was dissolved in 4% (w / v) ethanol solution under the condition of 65°C water bath as the water phase. Dissolve ICG (1 mg / ml) in 20% (v / v) methanol solution;

[0091] First, 100 μl of ICG solution was dropped dropwise into TPGS solution (2.5 ml) preheated in a 65° C. water bath under magnetic stirring. Subsequently, 500 μl of the oil phase solution was dropped into the TPGS solution drop by drop, and continued to stir for 20 minutes under the condition of a 35°C water bath to form uniform nanoparticles; the prepared nanoparticle solution was placed in an ultrafiltration centrifuge tube (molecular cut-off 10KDa), centrifuged at 4000rpm at 4°C for 20min,...

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Abstract

The invention provides a dual-functional nanoparticle, a soluble microneedle carrying the dual-functional nanoparticle and a preparing method and application. The dual-functional nanoparticle is higher in drug loading capacity and has duplex targeting capacity by adding cationic phospholipids and hyaluronic acid for modification. The dual-functional nanoparticle is composed of a polylactic acid-glycolic acid copolymer, vitamin E succinate, cationic phospholipids, a photosensitizer and a chemotherapy drug. The soluble microneedle is composed of a nanoparticle carrying needle and a substrate. The needle is made of polyvinyl alcohol and povidone, and the substrate is made of polyvinylpyrrolidone. Compared with traditional intratumor injection and tail vein injection, the soluble microneedle carrying the dual-functional nanoparticle and prepared through a multi-step centrifugal method has higher photo-thermal and tumor inhibition effects, and an effective scheme is provided for photo-thermal and chemotherapy combined treatment of superficial tumors.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a bifunctional nanoparticle, a corresponding soluble microneedle, a preparation method and application thereof. Background technique [0002] Tumor has become a major disease that endangers human health and causes human death. Superficial tumor (Superficialtumor, ST) is the most common type of tumor. Breast cancer is one of the most common female malignant tumors clinically, with a high incidence rate, and it has shown a younger trend in recent years. Chemotherapy, surgery and radiotherapy are the three traditional treatment methods for tumor treatment. With the development of science and technology and the deepening of tumor research, some new treatment methods such as phototherapy have also shown good anti-tumor effects. However, a single treatment method often has defects such as systemic toxicity, drug resistance, and insignificant effect. Therefore, c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K47/24A61K47/22A61K41/00A61K31/337A61P35/00
CPCA61K9/5153A61K9/5123A61K9/0021A61K41/0052A61K31/337A61P35/00A61K2300/00A61M2037/0046A61K9/5161A61K9/5192A61K9/0004
Inventor 吴传斌黄瑶彭婷婷俸小芊潘昕
Owner SUN YAT SEN UNIV
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