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High-concentration loading gel of adriamycin medicine and preparation method of high-concentration loading gel

A doxorubicin, high-concentration technology, which is applied in the field of high-concentration loading gel of doxorubicin drug and its preparation, can solve the problems of difficulty in maintaining long-term use, low strength of Fmoc-F gel, limitation, etc. Highly controllable process, optimized self-assembly process, low degradation burden

Pending Publication Date: 2022-07-05
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the strength of the single-component Fmoc-F gel is low, and it is difficult to maintain long-term use, which limits its function.
In order to improve the strength of LMWG, it is a relatively simple and efficient physical method to prepare it into a double network hybrid gel (DN). See the report

Method used

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  • High-concentration loading gel of adriamycin medicine and preparation method of high-concentration loading gel
  • High-concentration loading gel of adriamycin medicine and preparation method of high-concentration loading gel
  • High-concentration loading gel of adriamycin medicine and preparation method of high-concentration loading gel

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Step 1, prepare the precursor solution of gelling agent and drug, including 20wt% Fmoc-F in DMSO solution, 4wt% ALG aqueous solution prepared by stirring at 80°C for 5h, 100mg / mL DOX in DMSO precursor solution, and 100mg H / mL DOX 2 O solution;

[0032] Step 2, take 50 μL of the DMSO solution of Fmoc-F and 150 μL of the DMSO solution of DOX, and stir evenly to obtain the DMSO precursor solution of Fmoc-F / DOX;

[0033] Step 3, place 450 μL DOX HO 2 O solution, added to the DMSO precursor solution of the above Fmoc-F / DOX;

[0034] Step 4, adding 250 μL of ALG aqueous solution dropwise with stirring to obtain semi-DN-DOX;

[0035] Step 5, stop stirring and drop in 100μL of 2mol / L Ca 2+ The aqueous solution was allowed to stand to form a gel to obtain DN-DOX with a Fmoc-F content of 1 wt%, an ALG content of 1 wt%, and a total DOX loading of 60 mg / mL.

[0036] like Figure 2-4 As shown, using an inverted microscope (FLM, DMIRB, 20X) to observe the drug-loaded gel in Exa...

Embodiment 2

[0039] Step 1, prepare the precursor solution of gelling agent and drug, including 20wt% Fmoc-F in DMSO solution, 4wt% ALG aqueous solution prepared by stirring at 80°C for 5h, 100mg / mL DOX in DMSO precursor solution, and 100mg H / mL DOX 2 O solution;

[0040]Step 2, take 100 μL of the DMSO solution of Fmoc-F and 100 μL of the DMSO solution of DOX, and stir evenly to obtain the DMSO precursor solution of Fmoc-F / DOX;

[0041] Step 3, place 400 μL DOX in HO 2 O solution, added to the DMSO precursor solution of the above Fmoc-F / DOX;

[0042] Step 4, adding 250 μL of ALG aqueous solution dropwise with stirring, and adding 50 μL of water to obtain semi-DN-DOX;

[0043] Step 5, stop stirring and drop in 100μL of 2mol / L Ca 2+ The aqueous solution, standing to form a gel, is worth DN-DOX with a Fmoc-F content of 2 wt%, ALG content of 1 wt%, and a total DOX loading of 50 mg / mL.

Embodiment 3

[0045] Step 1, prepare the precursor solution of gelling agent and drug, including 20wt% Fmoc-F in DMSO solution, 4wt% ALG aqueous solution prepared by stirring at 80°C for 5h, 100mg / mL DOX in DMSO precursor solution, and 100mg H / mL DOX 2 O solution;

[0046] Step 2, take 50 μL of the DMSO solution of Fmoc-F and 150 μL of the DMSO solution of DOX, and stir evenly to obtain the DMSO precursor solution of Fmoc-F / DOX;

[0047] Step 3, place 450 μL of HO 2 O, add in the DMSO precursor solution of above-mentioned Fmoc-F / DOX;

[0048] Step 4, adding 250 μL of ALG aqueous solution dropwise with stirring to obtain semi-DN-DOX;

[0049] Step 5, stop stirring and drop in 100μL of 2mol / L Ca 2+ The aqueous solution, standing to form a gel, is worth DN-DOX with a Fmoc-F content of 1 wt%, ALG content of 1 wt%, and a total loading of DOX of 15 mg / mL.

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Abstract

The invention discloses a high-concentration doxorubicin drug loaded gel and a preparation method thereof. The high-concentration doxorubicin drug loaded gel is formed by co-assembling a hybrid dual-network gel carrier and a target drug doxorubicin hydrochloride in a one-pot system, the hybrid dual-network gel comprises a small molecular gelling agent component 9-fluorenylmethoxycarbonyl-L-phenylalanine and a polymer gelling agent component sodium alginate, a broad-spectrum cancer chemotherapy drug doxorubicin is taken as a loading target, the doxorubicin is pre-dissolved in different precursor solutions, then the precursor solutions are gradually added to participate in the assembling and forming process of a gel network, and the hybrid dual-network gel is obtained. According to the present invention, the controllable loading of the high-concentration DOX drug is achieved, the maximum loading capacity can achieve 60 mg / mL, the maximum loading rate can achieve 75%, the preparation method is simple and economical, the complex, high-toxicity and high-energy-consumption chemical synthesis or loading process is not involved, and the prepared drug-loaded gel has characteristics of large DOX loading capacity, highly controllable loading capacity, low carrier capacity, small degradation burden, and wide application prospect. And the injection has good characteristic of being injectable, and has good development prospect.

Description

technical field [0001] The invention belongs to the technical field of drug delivery carrier materials, relates to a doxorubicin drug carrier and a preparation method thereof, in particular to a high-concentration loaded gel of doxorubicin drug and a preparation method thereof. Background technique [0002] With the development of drug delivery carriers, it has gradually reached the degradable level, but increasing the drug loading still has important research significance for improving the effective delivery drug concentration and reducing the degradation burden. Doxorubicin (DOX) is a first-line chemotherapeutic drug with potent antitumor activity. However, clinically used doxorubicin injections can cause serious toxic side effects such as cardiotoxicity and bone marrow suppression. Traditional nano-drug delivery systems have poor affinity with drugs, resulting in low drug loading (usually less than 10%), poor stability, and easy drug leakage, resulting in low use efficie...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/36A61K47/18A61K47/20A61K31/704A61P35/00
CPCA61K9/06A61K47/36A61K47/183A61K47/20A61K31/704A61P35/00Y02P20/55
Inventor 杨鸿辉赵程程石博方王熖瑶延卫
Owner XI AN JIAOTONG UNIV
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