Integrin targeting drug loaded albumin nanoparticle formulation and its preparation method

A technology of albumin nanoparticles and albumin, which is applied in the field of gemcitabine albumin nanoparticles and its preparation, and integrin-targeted drug-loaded albumin nanoparticles preparations, which can solve the problem of inability to be used as a directional carrier and insufficient expression of pancreatic cancer cells. High, no specificity and other issues, to achieve good tumor targeting, improve treatment effect, reduce the effect of side effects

Inactive Publication Date: 2013-08-14
FUDAN UNIV SHANGHAI CANCER CENT
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] According to research, at present, orientation is mainly obtained through antibody-mediated, receptor-mediated, magnetism and pH sensitivity, among which antibody-mediated is mainly through antigen-antibody interaction, which is easy to cause human immune response, while magnetic and pH-sensitive The clinical application technology is still immature. In receptor-mediated guidance, researches on galactose, transferrin, folic acid, etc. have shown that the first two are not highly expressed in pancreatic cancer cells, have no specificity, and cannot be used as targeting carriers.

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  • Integrin targeting drug loaded albumin nanoparticle formulation and its preparation method
  • Integrin targeting drug loaded albumin nanoparticle formulation and its preparation method

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Embodiment 1

[0030]Example 1 Preparation of RGD-Coupled Gemcitabine Albumin Nanoparticles

[0031] Prepare 10ml of 3.0% BSA solution and adjust the pH to 8.5 with 1M NaOH. Add 40ml of absolute ethanol dropwise at a rate of 1ml / min under high-speed stirring until a blue gel-like solution is formed, and continue stirring for 60min. Add cross-linking agent glutaraldehyde (albumin amino molar ratio is 100%) under constant stirring, and continue stirring at a constant speed for 16-20 hours. Ethanol was removed by rotary evaporation at low temperature (40° C.), passed through a 1 μm filter membrane, and the remaining colloidal solution was centrifuged at 12,000 rpm for 10 minutes. The supernatant was removed, and the precipitated part was redissolved with distilled water to obtain a suspension of albumin nanoparticles. Take 5mg of RGD polypeptide, take a small amount from it and place it in a sterilized 1.5ml centrifuge tube, use 100μl double distilled water to try to dissolve the polypeptide,...

Embodiment 2

[0033] Example 2 RGD-Coupled Gemcitabine Albumin Nanoparticles Pairs Expressing Different Integrin α v beta 3 Pancreatic Cancer Cell Line Inhibition Experiment

[0034] The positive expression rates of integrin αvβ3 receptors on the surface of PANC-1, BxPC-3, SW1990, and CFPAC-1 cell lines in logarithmic growth phase were 13.58%, 86.94%, 71.50%, and 12.51%, respectively. The adherent cultured pancreatic cancer cell lines in the logarithmic growth phase were digested with 0.05% trypsin, and made into single-cell suspension with RPMI 1640 culture medium containing 10% calf serum. 3 The cells were inoculated into the wells of 96-well culture plates, with a volume of 200 μl per well. Move the culture plate to CO 2 In an incubator at 37°C, 5% CO 2 And greater than 95% humidity after cultivating for 24 hours, the cells adhered to the wall, and the cells were nearly fused. The culture solution was sucked out, and the RPMI 1640 culture solution containing 0.2% calf serum was left ...

Embodiment 3

[0035] Example 3 Tissue Drug Concentration Distribution of RGD-Coupled Gemcitabine Albumin Nanoparticles in Nude Mouse Implanted Tumor Model

[0036] Fifteen tumor-bearing nude mice were selected and randomly divided into 3 groups: GEM original drug group, BSANP-GEM group, and RGD-BSANP-GEM group. They were injected into the tail vein, and the dosage was calculated as GEM, which was GEM 90 mg / kg. 30 minutes after the administration, the nude mice were killed, and two pieces of tumor tissue, liver, kidney, spleen, pancreas, heart, and muscle tissue of 0.5 cm*0.5 cm were collected respectively. After the tissue was homogenized, the concentration of gemcitabine in the tissue was detected by HPLC. Chromatographic conditions:: chromatographic column: Phenomenex C18 (250mm×4.6mm, 4μm); column temperature: 45°C; mobile phase: acetonitrile-0.1% trifluoroacetic acid solution (3:97, v / v); flow rate: 1.0mL / min; UV detection wavelength: 268nm; injection volume: 100μL. The drug concentr...

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Abstract

The invention belongs to the field of medical technology and relates to an integrin targeting drug loaded albumin nanoparticle formulation and its preparation method. According to the invention, a gemcitabine-carried albumin nanoparticle target administration system is prepared by gemcitabine raw medicine, bovine serum albumin BSA, a RGD polypeptide, injection water, a dehydrating agent, a cross-linking agent and sodium hydroxide. The drug-loaded albumin nanoparticles have good dispersibility with a distribution range of particle size being 94-166nm, average particle size being 130nm, Zeta potential being -30.77mV, an encapsulation efficiency being 92.16%, a drug loading capacity being 12.8%, 30min burst release rate being 53.25+/-2.23% and 8 hours in vitro cumulative release rate reaching 90%. It is verified through experiments that the targeted nanoparticles provided by the invention can significantly increase the drug accumulation in the target sites, have good slow release and tumor targeting effects, can improve therapeutic effects and relieve toxic and side effects of chemotherapeutic drugs and enhance the tolerance of patients to treatment.

Description

technical field [0001] The invention belongs to the technical field of doctors, and relates to an integrin-targeted drug-loaded albumin nanoparticle preparation, in particular to an integrin-mediated gemcitabine albumin nanoparticle with targeted anti-tumor and its preparation method and application. Background technique [0002] Studies have shown that pancreatic cancer has a high degree of malignancy, and its morbidity and mortality are close. With the improvement of people's living standards, the morbidity is increasing year by year. According to reports, in 2002, the number of new cases of pancreatic cancer in the world was 232,300, and the death cases reached 227,000. There were 8,190 cancer cases, the total incidence rate was 12.17 / 100,000, and the standardized incidence rate was 6.22 / 100,000; pancreatic cancer ranked the 8th among males and the 7th among females in Shanghai, and the male-to-female incidence ratio was 1.18:1; 1973 From 2006 to 2006, the standardized i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K47/42A61K31/7068A61P35/00
Inventor 虞先濬徐近吉顺荣王浩龙江刘辰张波徐永锋姚宛彤许文彦
Owner FUDAN UNIV SHANGHAI CANCER CENT
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