Multistage response injectable hydrogel loaded with gambogic acid and application thereof

A technology of hydrogel and gambogic acid, which is applied in the field of multi-level response injectable hydrogel loaded with gambogic acid, which can solve the problem of low water solubility of gambogic acid, strong vascular irritation, and limitations of gambogic acid in clinical applications, etc. problem, to achieve the effect of improving drug loading capacity, less toxic and side effects, and good injectability

Active Publication Date: 2022-07-22
SICHUAN ACADEMY OF MEDICAL SCI SICHUAN PROVINCIAL PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are currently related studies ([1]L.Liu, X.J.Qi, Z.K.Zhong, et al. Nanomedicine-based combination of gambogic acid and retinoic acid chlorochalcone for enhanced anticancer efficacy in osteosarcoma[J].Biomedecine&pharmacotherapy, 2016(83):79- 84.[2]Z.F.Xin,C.C.Shen,L.J.Tao,et al.Gambogic acid inhibits invasion of osteosarcoma via upregulation ofTIMP-1[J].International

Method used

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  • Multistage response injectable hydrogel loaded with gambogic acid and application thereof
  • Multistage response injectable hydrogel loaded with gambogic acid and application thereof
  • Multistage response injectable hydrogel loaded with gambogic acid and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Embodiment 1, the preparation of the hydrogel of the present invention

[0046] 1. Synthesis and purification of polyethylene glycol-modified gambogic acid (GM)

[0047] (1) Gambogic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) dissolved in CH 2 Cl 2 In an ice-water bath, polyethylene glycol (weight average molecular weight 2000) was added. The resulting mixture was stirred at room temperature overnight.

[0048] (2) Wash with HCl, water, saturated brine, and use Mg 2 SO 4 Dry and concentrate in vacuo. The precipitate was stirred in ether to remove free gambogic acid. The solution was filtered to give a yellow precipitate.

[0049] (3) The crude product was further purified by silica gel column chromatography, in CH 2 Cl2 The free polyethylene glycol was removed by a step gradient of methanol, and the polyethylene glycol-modified gambogic acid (GM) was obtained as a light yellow solid.

[0050] 2. Preparation of Gam...

experiment example 1

[0063] Experimental example 1. Investigation on the gelation time of the hydrogel

[0064] 1. Experimental method

[0065] GA@LPS was prepared by referring to the preparation method of Example 1, and fibrinogen was dissolved in physiological saline to obtain four different concentrations of fibrinogen solutions (2 mg / ml, 5 mg / ml, 10 mg / ml and 20 mg / ml). Then, different concentrations of fibrinogen were mixed with an equal volume (1:1 volume ratio) of thrombin solution (10 NIH U / mL and 40 μmol / mL of calcium hydrogen phosphate nanowires) respectively, and three parallel experimental groups were set up for each concentration. The turbidity change of each group of solutions was measured immediately at a wavelength of 550 nm using a VersaMax UV-Vis spectrophotometer (Molecular Devices, Sunnyvale, CA), and the gelation time was defined as the time when the absorbance curve reached a maximum value.

[0066] 2. Experimental results

[0067] The result is as figure 1 As shown, it ca...

experiment example 2

[0068] Experimental example 2. Research on the synergistic effect of hydrogel gambogic acid and calcium hydrogen phosphate of the present invention

[0069] 1. Experimental method

[0070] Since calcium hydrogen phosphate nanowires have certain problems in the dispersion in aqueous solution and are easy to settle, the hydrogel of the present invention adopts the method of in situ administration of tumors, and calcium hydrogen phosphate is degraded in the slightly acidic environment of tumors to release Ca. 2+ , so in the systematic study of gambogic acid and calcium hydrogen phosphate in cell experiments, CaCl was used. 2 Substitute calcium hydrogen phosphate (CP) as calcium source.

[0071] Specifically, carried out:

[0072] (1) Calcium ion staining experiment:

[0073] The experiment was carried out when the K7M2 cells grew well and the density was above 85%. First, K7M2 cells were digested, resuspended, and counted, and then seeded in 6-well plates, 2 × 10 cells per we...

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Abstract

The invention provides a hydrogel precursor and hydrogel formed by curing the hydrogel precursor. The hydrogel precursor comprises the following components: 0.3-0.8 mg/mL of gambogic acid lipidosome; 3 to 8 mg/mL of fibrinogen; 3 to 8 NIHU/mL of thrombin; calcium hydrogen phosphate is 15 to 25 [mu] mol/mL; and the balance of water. The precursor has good injectable performance, hydrogel can be formed through physiological response solidification after local injection at a tumor site, in a tumor acid environment, medicine gambogic acid and calcium ions are released after a hydrogel skeleton containing calcium hydrophosphate is hydrolyzed, on one hand, gambogic acid has an anti-tumor effect, and on the other hand, the calcium ions can be released through calcium ions; on the other hand, hydrolyzed calcium ions can be promoted to enter tumor cells, calcium overload in the tumor cells is caused, apoptosis is caused, and therefore the synergistic effect is achieved for treating tumors. The hydrogel disclosed by the invention can improve the drug concentration of a tumor part through local in-situ injection, and is small in toxic and side effects, excellent in anti-tumor effect and good in clinical application prospect.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a multi-level response injectable hydrogel loaded with gambogic acid and uses thereof. Background technique [0002] Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents, accounting for about 30% of all bone cancers, and is currently the most common malignant tumor causing death in children and adolescents. Osteosarcoma is characterized by tumor metastasis, differentiation into cartilage and bone. Despite major advances in the treatment of most primary osteosarcomas, the 5-year survival rate is still around 60%, and the survival rate for metastatic tumors is only 20%. The current clinical standard treatment strategies are surgery, radiotherapy and adjuvant chemotherapy. Especially in the early stage of osteosarcoma, chemotherapy drugs such as methotrexate, ifosfamide, doxorubicin and cisplatin are the first choice to control the g...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K9/127A61K31/352A61K33/42A61K47/02A61K47/42A61K47/60A61P35/00
CPCA61K31/352A61K33/42A61K9/0024A61K9/06A61K9/127A61K47/60A61K47/42A61K47/02A61P35/00A61K2300/00Y02A50/30
Inventor 蔡璐璐杨磊何林童荣生
Owner SICHUAN ACADEMY OF MEDICAL SCI SICHUAN PROVINCIAL PEOPLES HOSPITAL
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