an integrin a v beta 3 Targeted drug carrier and preparation method thereof

A targeted drug delivery and integrin technology, applied in the field of biomedicine, can solve the problem of low targeting of tumor cells, achieve the effects of prolonging circulation time, reducing cytotoxicity and hemolytic toxicity, and improving hydrophilicity

Inactive Publication Date: 2016-09-14
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Technical problem to be solved: the present invention mainly solves the problem of low targeting of PAMAM-SS-PEG to tumor cells, and designs a PAMAM-based integrin a v beta 3 Targeted drug delivery carrier and preparation method thereof, so as to improve the antitumor effect of medicine

Method used

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  • an integrin a <sub>v</sub> beta <sub>3</sub> Targeted drug carrier and preparation method thereof
  • an integrin a <sub>v</sub> beta <sub>3</sub> Targeted drug carrier and preparation method thereof
  • an integrin a <sub>v</sub> beta <sub>3</sub> Targeted drug carrier and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Dissolve 5 mg of PAMAM (generation 4) in 1.5 mL of methanol solution, add 3.5 mg of SPDP, and stir for 5 h at 30 °C in the dark to generate the PAMAM-NH-SPDP intermediate; the resulting PAMAM-NH-SPDP In the intermediate, the molar ratio of PAMAM to SPDP is 1:32. Add 56 mg of HS-(CH 2 CH 2 O) 112 -CH 2 COOH, stirred overnight, the resulting product was transferred to a dialysis bag (MW: 8000-14000), dialyzed in water for 2 days, freeze-dried for 3 days to obtain a white solid PAMAM-SS-PEG 32 ,Keep away from light. Take 20 mg of PAMAM-SS-PEG 32 Dissolve in 2 ml of DMSO, add 3.4 mg of EDC and 2 mg of NHS to react for 30 min, then add 2.16 mg of cRGDyK at a molar ratio of 1:32, continue to react for 6 h, and dialyze the obtained product (MW: 3500) , the freeze-dried white solid is PAMAM-SS-PEG-RGD polymer, and its yield is about 81.6%, (X=112, Y=32, Z=32).

[0042] Carry out nuclear magnetic analysis to the product synthesized in embodiment 1, the result is as follo...

Embodiment 2

[0058] Dissolve 5 mg of PAMAM (generation 10) in 1.5 mL of methanol solution, add 0.02 mg of SPDP, and stir for 5 h at 30 °C in the dark to generate a PAMAM-NH-SPDP intermediate; the resulting PAMAM-NH-SPDP In the intermediate, the molar ratio of PAMAM to SPDP is 1:1. Add 0.05 mg of HS-(CH 2 CH 2 O) 20 -CH 2 COOH, stirred overnight, the obtained product was transferred to a dialysis bag (MW: 8000-14000), dialyzed in water for 2 days, and freeze-dried for 3 days to obtain a white solid called PAMAM-SS-PEG, which was stored in the dark. Dissolve 20 mg of PAMAM-SS-PEG in 2 ml of DMSO, add 0.03 mg of EDC and 0.06 mg of NHS to react for 30 min, then add 0.36 mg of cRGDyK according to the molar ratio of the two at 1:1, and continue the reaction for 6 h. The obtained product was dialyzed (MW: 3500) and freeze-dried to obtain a white solid, which was PAMAM-SS-PEG-RGD polymer, and the yield was about 78.1%, (X=20, Y=1, Z=1).

Embodiment 3

[0060] Dissolve 5 mg of PAMAM (generation 10) in 1.5 mL of methanol solution, add 6.8 mg of SPDP, and stir at 30 °C for 5 h in the dark to generate a PAMAM-NH-SPDP intermediate; the resulting PAMAM-NH-SPDP In the intermediate, the molar ratio of PAMAM to SPDP is 1:4096. Add 966 mg of HS-(CH 2 CH 2 O) 1000 -CH 2 COOH, stirred overnight, the resulting product was transferred to a dialysis bag (MW: 8000-14000), dialyzed in water for 2 days, freeze-dried for 3 days to obtain a white solid PAMAM-SS-PEG 4096 ,Keep away from light. Take 20 mg of PAMAM-SS-PEG 4096 Dissolve in 2 ml of DMSO, add 43 mg of EDC and 252 mg of NHS to react for 30 min, then add 0.07 mg of cRGDyK according to the molar ratio of 4096:1, continue to react for 6 h, and dialyze the obtained product (MW: 3500) , the white solid obtained by lyophilization is PAMAM-SS-PEG-RGD polymer, and the yield is about 68.6%, (X=1000, Y=4096, Z=1).

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Abstract

The invention discloses a PAMAM-based integrin a v beta 3 Targeted drug delivery carrier, the general structural formula is: The preparation method of the drug delivery carrier is firstly linking PAMAM and polyethylene glycol through a reduction-sensitive disulfide bond to form a reduction-sensitive polymer carrier (PAMAM-SS-PEG), and secondly, separating the polyethylene glycol in the carrier integrin a v beta 3 Targeting functional groups to form both reduction-sensitive and integrin-a v beta 3 Targeted PAMAM dendrimer carrier (PAMAM‑SS‑PEG‑T). The drug delivery carrier of the present invention can circulate in the blood for a long time, and can enhance the ability of integrin a v beta 3 The uptake of the polymer by the tumor cells of the receptor can realize the active targeting and passive targeting of the tumor tissue. In addition, under the conditions of high reducing environment and low pH in tumor cells, the disulfide bond in the carrier breaks, and at the same time, the inner core of PAMAM opens, so that the drug can be released quickly and effectively, so as to improve the therapeutic effect of anti-tumor drugs and The purpose of reducing toxic side effects.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to a targeted drug delivery carrier and a preparation method thereof, in particular to a PAMAM-based integrin a v beta 3 Targeted drug delivery carrier and preparation method thereof. Background technique [0002] According to the "2013 China Cancer Registration Annual Report" released by the National Cancer Registration Center in 2014, there are about 3.12 million new cancer cases in my country every year, with an average of 8,550 people getting sick every day, that is, 6 people are diagnosed every minute For cancer, 5 people died of cancer, and cancer has become the second most serious disease that threatens human health except cardiovascular and cerebrovascular diseases. At present, chemotherapy is still used clinically as one of the main methods of cancer treatment, but due to the toxic effect of the drug itself, cells in the body will be destroyed regardless of whether they ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/34A61P35/00C08G81/00
Inventor 程亮胡文程丽芳陈大为
Owner SUZHOU UNIV
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