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Tussah silk protein adriamycin sustained release microsphere and preparation method thereof

A technology of tussah silk fibroin and slow-release microspheres, which is applied in the field of biomedicine, can solve the problems of large diameter of microspheres, influence on drug activity and albumin activity, low drug loading rate and embedding rate, and reduce toxic and side effects , the effect of improving efficiency

Inactive Publication Date: 2015-03-25
SUZHOU UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Chinese invention patent (CN10569609A) prepares albumin doxorubicin granules by ultrasonic atomization method, the particle diameter is large, cross-linking by heating and adding chemical cross-linking agent may affect the activity of the drug and the activity of albumin
The document "Journal of Nano Research, 2014, 27: 75-81" introduces a kind of tussah silk fibroin protein-loaded doxorubicin drug microspheres under different pH conditions, and doxorubicin hydrochloride is dissolved in a buffer solution with pH=4.3, Then the silk fibroin is blended with the buffer solution, and this method is used to prepare tussah silk fibroin microspheres loaded with doxorubicin. The particle size of the microspheres is about 4um, which has a good tumor targeting effect, but The drug loading rate is low and the embedding rate is low, and the diameter of the microsphere is large

Method used

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  • Tussah silk protein adriamycin sustained release microsphere and preparation method thereof
  • Tussah silk protein adriamycin sustained release microsphere and preparation method thereof
  • Tussah silk protein adriamycin sustained release microsphere and preparation method thereof

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Embodiment 1

[0024] Put 80g tussah silk in the environment of 98~100℃, put it in the 2 CO 3 and 0.0625g / L sodium lauryl sulfate solution for degumming 3 times, 30min each time, bath ratio 1:50. After degumming, the tussah silk fibers are obtained and dried at 60°C. Put the tussah silk fibroin fiber in a saturated lithium thiocyanate solution at a bath ratio of 1:10, and dissolve it for 60 minutes at 50°C±2°C. In the dialysis bag, dialyze with deionized water for 4 days, then centrifuge to obtain a regenerated tussah silk fibroin protein solution with a mass concentration of about 30 mg / ml, and put it in a refrigerator at 4°C for later use.

[0025] Adjust the concentration of tussah silk fibroin protein to 10 mg / ml, configure doxorubicin hydrochloride solution, the concentration is 10 mg / ml; configure calcium chloride solution, the concentration is 100 mmol per liter; add doxorubicin hydrochloride solution to tussah silk Stir mechanically in the protein solution to fully disperse doxor...

Embodiment 2

[0033] Put 120g of tussah silk in a stainless steel pot of 4L of deionized water, heat it to boiling with an induction cooker, add 0.06% Na 2 CO 3 In aqueous solution, degumming 3 times, 35min each time, bath ratio 1:60. After degumming, the tussah silk fibers are obtained and dried at 60°C. Put the tussah silk fibroin fiber in a saturated lithium thiocyanate solution at a bath ratio of 1:10, dissolve it for 70 minutes at 50°C±2°C, and put the obtained tussah silk fibroin protein solution into a dialyzer with a molecular weight cut-off of 8-10 KDa bag, dialyzed with deionized water for 4 days, and then centrifuged to obtain a regenerated tussah silk fibroin protein solution with a mass concentration of about 25 mg / ml, and put it in a refrigerator at 4°C for later use.

[0034] Adjust the concentration of tussah silk fibroin protein to 20 mg / ml, configure doxorubicin hydrochloride solution, the concentration is 10 mg / ml; configure calcium nitrate solution, the concentration i...

Embodiment 3

[0036] Put 180 grams of tussah silk into 8L of 0.05% sodium carbonate aqueous solution, degumming at 98-100° C. for 0.5 hour, repeat the treatment 3 times, and obtain pure tussah silk fibroin fiber after fully washing. The tussah silk fibroin protein mixed solution is obtained by heating and dissolving the dried tussah silk fibers with 1 liter of lithium thiocyanate solution with a concentration of 9.3 mol / liter at 55±5° C. The cellulose membrane is used as a dialysis material, and the obtained tussah silk fibroin protein mixed solution is dialyzed with deionized water for 3 days to obtain a pure tussah silk fibroin protein solution.

[0037] Adjust the concentration of tussah silk fibroin protein to 30 mg / ml, configure doxorubicin hydrochloride solution, the concentration is 10 mg / ml; configure calcium gluconate solution, the concentration is 100 mmol per liter; add doxorubicin hydrochloride solution to tussah silk Mechanically stir in the protein solution to fully disperse d...

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Abstract

The invention discloses a tussah silk protein adriamycin sustained release microsphere and a preparation method thereof. The tussah silk protein adriamycin sustained release microsphere takes calcium ions as an inducer, natural tussah silk proteins as a shell and adriamycin as nano particles of a core, is uniform in distribution of particle sizes, has the diameter of about 500 nanometers and is biodegradable. According to the tussah silk protein adriamycin sustained release microsphere and the preparation method disclosed by the invention, as the preparation environment of the tussah silk protein adriamycin sustained release microsphere is in a neutral and normal pressure and temperature state, an organic solvent is avoided, and the utilization degree of a medicament is increased; with the tussah silk proteins as an embedding material of the adriamycin, the tussah silk protein adriamycin sustained release microsphere has an RGD sequence and is capable of promoting cells to identify the tussah silk protein adriamycin sustained release microsphere and improving the targeting property of an adriamycin medicament; compared with free adriamycin, the adriamycin embedded in the tussah silk protein microsphere is obvious in sustained release property, expresses pH sensitivity, is obvious in sustained release effect in the environment with a pH value of 5.2, is small in releasing speed under the neutral condition, is convenient for a medicament to be released after entering cancer cells and is capable of remarkably lowering the toxic and side effects in normal cells.

Description

technical field [0001] The invention relates to a drug-loaded microsphere and a preparation method thereof, in particular to a microsphere prepared from tussah silk fibroin-doxorubicin hydrochloride as a raw material and a preparation method thereof, belonging to the technical field of biomedicine. Background technique [0002] Malignant tumor is a common and frequently-occurring disease that seriously threatens human health. At present, there is no effective prevention and control measure. The main method of clinical treatment of cancer is radiotherapy and chemotherapy, but the antitumor drugs used in chemotherapy have serious toxic and side effects on normal organs of the human body. The targeted drug delivery system delivers the drug directly to the lesion site through the carrier material to exert its curative effect. It has the advantages of strong specificity, low toxicity and side effects, improved drug efficacy, reduced drug dose and frequency of administration, etc...

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K31/704A61K47/48A61P35/00
Inventor 王娟卢神州殷祝平邢铁玲
Owner SUZHOU UNIV
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