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CN-117084996-B - Curcumin composite nanoparticle with stable drug loading and preparation method thereof

CN117084996BCN 117084996 BCN117084996 BCN 117084996BCN-117084996-B

Abstract

The invention relates to the technical field of drug-loaded particles and discloses a curcumin composite nanoparticle with stable drug loading and a preparation method thereof, wherein a rice protein hydrolysate is used as a carrier to load curcumin, and chondroitin sulfate is used for stabilizing the rice protein hydrolysate to load the curcumin, the encapsulation rate of the curcumin composite nanoparticle is 70% -90%, the mass ratio of the contained rice protein hydrolysate to the chondroitin sulfate is 1-5:1, and the mass ratio of the contained rice protein hydrolysate to the curcumin is 8-12:1. When the nanoparticle is dissolved in gastric acid with the pH value of 0.9-1.5, the protein in the nanoparticle still keeps stable, the larger curcumin retention rate can still be kept, the particle size is also kept at the nanoscale, the nanoscale particle size also enables the nanoparticle to be easily absorbed by intestinal cells, and the bioavailability is effectively improved.

Inventors

  • JIAO YE
  • CHENG YUNHUI
  • CHEN XIUWEN
  • WEN LI
  • CUI BO

Assignees

  • 长沙理工大学
  • 齐鲁工业大学(山东省科学院)

Dates

Publication Date
20260512
Application Date
20230705

Claims (6)

  1. 1. The curcumin composite nanoparticle with stable drug loading is characterized by comprising the steps of taking rice protein hydrolysate as a carrier, loading curcumin, and stabilizing the rice protein hydrolysate to load the curcumin by using chondroitin sulfate, wherein the encapsulation rate of the curcumin composite nanoparticle is 70% -90%, the mass ratio of the contained rice protein hydrolysate to the chondroitin sulfate is 1-5:1, and the mass ratio of the contained rice protein hydrolysate to the curcumin is 8-12:1; The curcumin composite nano-particle has stable suspension property and more than 85 percent of curcumin retention rate in an environment of room temperature to 80 ℃, and the particle size of the curcumin composite nano-particle is less than or equal to 300nm when the pH value is lower than 2; the particle size of the nano particles is 100-190 nm, and the Zeta potential is-20 to-30 mV.
  2. 2. The method for preparing the curcumin composite nanoparticle with stable drug loading according to claim 1, which is characterized by comprising the following steps: 1) Preparing aqueous solution from rice protein hydrolysate, preparing aqueous solution from chondroitin sulfate, and mixing and stirring to form aqueous solution of rice protein hydrolysate-chondroitin sulfate binary composite nano carrier; 2) Dripping the curcumin ethanol solution into the rice protein hydrolysate-chondroitin sulfate binary composite nano-carrier aqueous solution prepared in the step 1), and adjusting the pH value to 3-7 to obtain a mixed solution; 3) And (3) performing rotary evaporation, constant volume and centrifugation on the mixed solution prepared in the step (2) to remove sediment, and refrigerating the supernatant to obtain the curcumin composite nanoparticle.
  3. 3. The preparation method of the curcumin composite nanoparticle with stable drug loading according to claim 2, wherein the mass concentration of the aqueous solution of the rice protein hydrolysate in the step 1) is 0.8-1.5 mg/mL, the mass concentration of the aqueous solution of the chondroitin sulfate is 0.8-1.5 mg/mL, and the mixing mass ratio of the rice protein hydrolysate and the chondroitin sulfate is controlled to be 1-5:1.
  4. 4. The preparation method of the curcumin composite nanoparticle with stable drug loading according to claim 2, wherein the mass concentration of the curcumin ethanol solution in the step 2) is 0.8-1.5 mg/mL, and the mixing mass ratio of the rice protein hydrolysate and the curcumin is controlled to be 8-12:1.
  5. 5. The method for preparing curcumin composite nano-particles with stable drug loading according to claim 2, wherein in the step 3), the spin steaming temperature is 35-40 ℃, the centrifugal speed is 7000-10000 Xg, and the refrigerating temperature is 3-5 ℃.
  6. 6. An oral drug made of the curcumin composite nanoparticle with stable drug loading according to claim 1 or the curcumin composite nanoparticle with stable drug loading prepared by the preparation method of the curcumin composite nanoparticle with stable drug loading according to any one of claims 2-5.

Description

Curcumin composite nanoparticle with stable drug loading and preparation method thereof Technical Field The invention relates to the technical field of drug-loaded particles, in particular to a curcumin composite nanoparticle with stable drug loading and a preparation method thereof. Background Curcumin has wide physiological activities including antioxidation, anti-inflammation, anti-cancer, anti-tumor, anti-lipid metabolism abnormality and the like, has been allowed to be applied to health care foods by relevant institutions and countries such as European Union and China as a functional ingredient, however, the bioavailability and the exertion of potential health effects are greatly limited due to the limitations of low water solubility (the solubility in water is only 11 ng/mL), poor stability (degradation or loss of physiological activity is easily caused by the influence of processing conditions such as pH, temperature, oxygen, illumination and the like and environmental factors) and rapid metabolism rate (the physiological barrier is difficult to penetrate in vivo and the liver is easy to metabolize or clear). The complex nano carrier matrix formed by the interaction of the Protein and the polysaccharide can be helpful for further improving the encapsulation capacity, the protection effect and the bioavailability of bioactive substances, and Rice Protein (RP) is a recognized high-quality plant Protein and has the advantages of balanced amino acid composition, high biological titer, high Protein utilization rate, low sensitization and the like. But the solubility of the main component gluten of the rice protein is low due to the existence of a large amount of disulfide crosslinking and hydrophobic effects, so that the large-scale commercial application of the main component gluten of the rice protein in the food industry field is limited. Through enzymolysis modification of rice protein, not only can the solubility be effectively improved, but also the obtained rice protein zymolyte (Rice Protein Hydrolysate, RPH) has proved to have application potential as a nano carrier of bioactive substances. However, rice protein hydrolysate nano-carriers have poor stability in terms of coping with environmental changes, and the addition of polysaccharides is expected to improve the performance and stability thereof. Chondroitin sulfate (Chondroitin sulfate, cs) is a sulfated glycosaminoglycan composed of n-acetylgalactosamine and glucuronic acid, has various physiological activities such as anti-inflammatory, antioxidant and immunomodulating, and is used as a nutritional supplement and an over-the-counter medicine for treating osteoarthritis. At present, chondroitin sulfate has been proved to be capable of effectively improving the encapsulation and protection effects of protein-based nano-carriers such as zein, gliadin and the like on bioactive substances. The prior patent application number 202110432458.4 in China discloses a high-load and high-stability protein-based curcumin product, a preparation method and application thereof, and uses basic protein as a carrier to load curcumin to improve the solubility, suspension stability and biocompatibility of curcumin in water, but the patent does not notice that the curcumin is absorbed by human bodies through intestines and stomach, when the particle size of the curcumin product is overlarge, the absorption rate of gastrointestinal cells can be obviously reduced, and a lot of basic proteins are easy to denature under the action of gastric acid, are difficult to keep stable, so that the built-in curcumin is released in advance, and the bioavailability of the curcumin is poor. Disclosure of Invention Aiming at the problem that bioavailability is not considered when curcumin solubility is improved in the prior art, the invention provides a curcumin composite nanoparticle with stable drug loading, which has the characteristics of small particle size, high solubility, good dispersibility and easy absorption by intestinal cells. The invention is realized by the following technical scheme: The curcumin composite nanoparticle with stable drug loading comprises the steps of taking rice protein hydrolysate as a carrier, loading curcumin, and stabilizing the rice protein hydrolysate to load the curcumin by using chondroitin sulfate, wherein the encapsulation rate of the curcumin composite nanoparticle is 70% -90%, the mass ratio of the contained rice protein hydrolysate to the chondroitin sulfate is 1-5:1, and the mass ratio of the contained rice protein hydrolysate to the curcumin is 8-12:1. The nano particles can be dissolved in water for a long time to keep suspension and dispersion, are not easy to agglomerate and precipitate, so that more curcumin is dissolved in water and is easy to be absorbed by gastrointestinal tract, meanwhile, the nano particles are stable in an acidic to neutral environment, which means that when dissolved in gastric acid with the pH value of 0.9-