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Albumin nanoparticles realizing co-delivery of antitumor drug and MRI (magnetic resonance imaging) contrast medium and preparation method of albumin nanoparticles

A technology of albumin nanoparticles and anti-tumor drugs, applied in anti-tumor drugs, MRI/magnetic resonance imaging contrast agents, pharmaceutical formulations, etc. To avoid toxicity and reverse tumor drug resistance

Active Publication Date: 2016-08-24
CHINA PHARM UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

MnO 2 Relaxation efficiency (r 1 ) is low and cannot be used as an MRI contrast agent; after being reduced to manganese ions, the distance between its paramagnetic center (manganese ions) and water molecules decreases, r 1 increase, T 1 Increased weighted imaging capabilities

Method used

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  • Albumin nanoparticles realizing co-delivery of antitumor drug and MRI (magnetic resonance imaging) contrast medium and preparation method of albumin nanoparticles
  • Albumin nanoparticles realizing co-delivery of antitumor drug and MRI (magnetic resonance imaging) contrast medium and preparation method of albumin nanoparticles
  • Albumin nanoparticles realizing co-delivery of antitumor drug and MRI (magnetic resonance imaging) contrast medium and preparation method of albumin nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0042] (1) BSA-MnO 2 Solution preparation: under stirring, Na at a constant rate 2 S 2 o 3 The solution was dropped into KMnO 4 In the solution, react under nitrogen protection at 4-30 °C for 1-4 hours to obtain MnO 2 Colloidal nanoparticle solution; MnO 2 Drop BSA solution into the colloidal nanoparticle solution, react for 6-24 hours at 4-30°C under nitrogen protection, and purify by dialysis with pure water to obtain a stable brown colloidal solution, namely BSA-MnO 2 solution;

[0043] (2) Desolvation-chemical cross-linking method to entrap antineoplastic drugs: add the antineoplastic drug solution to BSA-MnO dropwise according to a certain ratio 2 Add a certain volume of absolute ethanol dropwise to the solution, stir at 4-30°C for 10-60 minutes, add a cross-linking agent, seal and stir at 4-30°C for 6-24 hours, distill under reduced pressure to remove ethanol, and dialyze and purify That is, the antineoplastic drug and the MRI contrast agent co-deliver the albumin...

Embodiment 1

[0044] Embodiment 1: the preparation of BMDN

[0045] Prepare 0.3 mg / mL of Na 2 S 2 o 3 solution and 0.8 mg / mL of KMnO 4 Solution, 20mL Na 2 S 2 o 3 The solution was dropped into 10 mL KMnO 4 The solution was stirred at room temperature for 1 hour under the protection of nitrogen. 7.5 mL of BSA (25 mg / mL) was added dropwise to the reaction solution, and stirred at room temperature for 12 hours under nitrogen protection. The resulting product was dialyzed against pure water 4 times for half an hour each time.

[0046] Under stirring, DOX solution (5 mg / mL) was added dropwise to BSA-MnO according to the theoretical drug loading of 10%. 2 solution, and then immediately add 1 volume of absolute ethanol dropwise to the above solution. After stirring for 15 minutes, 0.25% glutaraldehyde was added to the system (0.367 μL glutaraldehyde per mg of BSA), the reaction bottle was sealed, and stirring was continued for 12 hours at room temperature. Ethanol was distilled off unde...

Embodiment 2

[0047] Example 2: BMDN pH-responsive drug release

[0048] Take 1.5 mL of BMDN solution in a dialysis bag, tie the bag tightly, and submerge it in an Erlenmeyer flask filled with 28.5 mL of phosphate buffer solution (pH 5.0 or 7.4). Then the Erlenmeyer flask was placed in a constant temperature shaker at 37 °C, shaking at 120 rpm. At specific time points, 3 mL of release medium was taken to measure the absorbance at 479 nm, and 3 mL of fresh phosphate buffer solution was added. Calculate the concentration of DOX in the release medium according to the standard curve, thereby calculating the release degree and drawing the release curve, the results are as follows figure 2 shown.

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Abstract

The invention discloses albumin nanoparticles realizing co-delivery of an antitumor drug and an MRI (magnetic resonance imaging) contrast medium and a preparation method of the albumin nanoparticles and further provides an albumin nanoparticle vector containing the MRI contrast medium, and drug loading is realized through electrostatic adsorption and coordination between the drug and the vector as well as crosslinking of amino acid residues of the vector. The invention further discloses an optimal preparation technology of the albumin nanoparticles realizing co-delivery of the antitumor drug and the MRI contrast medium and a function of the albumin nanoparticles in diagnosis and treatment combination of tumors. According to the albumin nanoparticles realizing co-delivery of the antitumor drug and the MRI contrast medium, the drug uptake ratio of cells can be increased, and drug efflux caused by drug-resistant cells is reduced, so that drug resistance is reversed, and efficient delivery of the drug is realized; the albumin nanoparticles realizing co-delivery of the antitumor drug and the MRI contrast medium have excellent T1 weighted imaging capability and an effective means is provided for the diagnosis and treatment combination of the tumors.

Description

technical field [0001] The invention relates to an antineoplastic drug and an MRI contrast agent co-delivering albumin nanoparticles, as well as an MRI contrast agent and a pharmaceutical composition containing the carrier, belonging to the technical field of drug carriers. Background technique [0002] Chemotherapy of tumors has achieved many great achievements in the past half century, and it has become one of the methods of treating tumors and an indispensable and important means in the comprehensive treatment of common tumors. However, the side effects and multidrug resistance associated with the treatment process have greatly hindered the clinical application of chemotherapy drugs. Nano-drug delivery systems can achieve reversal of drug resistance by circumventing or reducing the xenophobia of drug-resistant tumor cells. Compared with other carrier materials, albumin (BSA) has the advantages of non-toxicity, low antigenicity, and biodegradability, and the amino acid re...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K49/08A61K31/704A61K9/14A61P35/00
CPCA61K9/146A61K31/704A61K49/08
Inventor 姜虎林张美邢磊
Owner CHINA PHARM UNIV
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