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Dual drug-loaded red blood cell(RBC) carrier, preparation method and application thereof

A technology of red blood cells and dual drug loading, which is applied in the field of medicine, can solve the problems of limited efficacy of a single drug, achieve the effects of reducing the risk of drug resistance and side effects, simple preparation process, and economical raw materials

Active Publication Date: 2019-09-27
SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, in the treatment of many clinical diseases, the efficacy of a single drug is limited, and the combined treatment of two or more drugs has become an effective drug method.

Method used

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  • Dual drug-loaded red blood cell(RBC) carrier, preparation method and application thereof
  • Dual drug-loaded red blood cell(RBC) carrier, preparation method and application thereof
  • Dual drug-loaded red blood cell(RBC) carrier, preparation method and application thereof

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preparation example Construction

[0034] Another aspect of the embodiments of the present invention also provides a method for preparing the double drug-loaded erythrocyte carrier, which includes:

[0035] S1. Mix red blood cells derived from the blood of healthy adults with the first drug molecule solution, add hypertonic solution to reseal, and then undergo ultrasonic treatment to obtain red blood cells carrying the first drug molecule;

[0036] S2. Streptavidin is mixed with DSPE-PEG-biotin to obtain avidinized DSPE-PEG, and then mixed with the second drug molecule to obtain a conjugate of DSPE-PEG-second drug molecule;

[0037] S3. Mix the red blood cell solution loaded with the first drug molecule in step S1 with the DSPE-PEG-Cet in step S2, and continuously extrude through a polycarbonate porous membrane to obtain a double drug-loaded red blood cell carrier.

[0038] In some embodiments, the method of preparing the erythrocytes in step S1 is as follows: after anticoagulating the blood from a healthy adul...

Embodiment 1

[0056] Example 1: Preparation of double-loaded paclitaxel-cetuximab erythrocyte carrier (also known as "dual drug-loaded erythrocyte carrier" or "drug-loaded erythrocyte")

[0057] 1. Anticoagulate the blood from healthy adults with heparin, centrifuge to remove the upper plasma and buffy coat, wash with 1XPBS buffer (pH 7.3) for 4 times to obtain red blood cells, and then add pre-cooled Hypotonic solution (0.25XPBS buffer) was treated for 30 min, then centrifuged to remove hemoglobin, and washed until the supernatant was colorless, and the bottom erythrocyte precipitate was collected, wherein the volume ratio of erythrocytes to hypotonic solution was 1:4.

[0058] 2. Mix the red blood cell membrane and paclitaxel solution obtained in step 1 at a volume ratio of 1:2, then add hypertonic solution (10XPBS buffer) at 30°C, reseal for 40 minutes, then sonicate for 4 minutes, and centrifuge to remove free paclitaxel , to obtain paclitaxel-loaded erythrocytes, and store them at 4°C ...

Embodiment 2

[0070] Example 2: Preparation of erythrocyte carrier double loaded with paclitaxel-cetuximab

[0071] 1. After anticoagulation with heparin, the blood from healthy adults was centrifuged to remove the upper plasma and buffy coat, washed three times with 1XPBS buffer (pH 7.2) to obtain red blood cells, and then added pre-cooled Hypotonic solution (0.25X PBS buffer) was treated for 15 minutes, and then centrifuged to remove hemoglobin, and washed until the supernatant was colorless, and the red blood cell pellet at the bottom was collected, wherein the volume ratio of red blood cells to hypotonic solution was 1:2.

[0072] 2. Mix the erythrocyte membrane and paclitaxel solution obtained in step 1 at a volume ratio of 1:1, then add hypertonic solution (10X PBS buffer) at 25°C, reseal for 30 minutes, then sonicate for 3 minutes, and centrifuge to remove free Paclitaxel, the red blood cells loaded with paclitaxel were obtained and stored at 4°C for later use;

[0073] 3. Streptavi...

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Abstract

The invention discloses a dual drug-loaded RBC carrier and preparation method and application of the dual drug-loaded RBC carrier. The dual drug-loaded RBC carrier comprises RBC, first drug molecules encapsulated in RBCs, and second drug molecules coupled to the surfaces of RBCs. The first drug molecules may be paclitaxel (PTX) or the like, and the second drug molecules may be cetuximab (Cet) or the like. The dual drug-loaded RBC carrier disclosed by the invention utilizes RBC to simultaneously load two therapeutic molecules of the first drug molecules and the second drug molecules, and reduces drug resistance risks and toxic and side effects caused by drugs through entrapment of the RBC carrier on the one hand to increase the safety of administration, and further can exert better therapeutic effects on different problems through two different functions of drug loading on the other hand. Furthermore, the dual drug-loaded RBC carrier disclosed by the invention is simple in preparation process, economical and readily available in raw materials, does not need to rely on complicated equipments, and is easy to realize industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a double drug-loaded erythrocyte carrier and a preparation method thereof. Background technique [0002] Red blood cell (RBC) is a unique natural drug carrier. Since the 1970s, due to the many favorable properties of red blood cells in terms of biodegradation and release profile, they have been studied as drug delivery carriers for nearly half a century, and have successfully encapsulated various molecules, including antibodies / enzymes , polypeptides, nucleic acids, nanoparticles, and chemical drugs, etc., some of which have been successfully transformed into human clinical trials, such as L-asparaginase, dexamethasone, etc. However, the current use of erythrocytes as carriers is mostly limited to carrying a single molecule in the erythrocyte or coupled to the surface of the erythrocyte membrane. [0003] Paclitaxel (PTX), a diterpene taxane, is commonly used clini...

Claims

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Application Information

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IPC IPC(8): A61K9/50A61K47/46A61K47/60A61K31/337A61K39/395A61P35/00A61P25/00
CPCA61K9/5068A61K31/337A61K39/395A61K47/60A61P25/00A61P35/00A61K2300/00
Inventor 戴建武胡玲玲陈艳艳
Owner SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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