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Micelles, nucleic acid delivery system and nasal mucosa drug delivery system

A nucleic acid delivery and micelle technology, applied in the field of biomedicine, can solve the problem of less research in the field of nasal mucosal drug delivery, achieve significant anti-tumor effect, reduce systemic side effects, and low cytotoxicity.

Pending Publication Date: 2022-04-15
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although the current research on siRNA delivery vehicles has achieved certain effects in intravenous administration, subcutaneous administration, intratumoral administration, etc., there are still few studies in the field of nasal mucosal administration.

Method used

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  • Micelles, nucleic acid delivery system and nasal mucosa drug delivery system
  • Micelles, nucleic acid delivery system and nasal mucosa drug delivery system
  • Micelles, nucleic acid delivery system and nasal mucosa drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0115] Example 1. Preparation and characterization of DP7-C / siRNA complex

[0116] In this example, we used the electrostatic adsorption method to prepare the DP7-C / siRNA complex.

[0117] 1. Preparation and characterization of DP7-C / siRNA complex.

[0118] Weigh 10 mg of DP7-C powder, dissolve it in MilliQ water, and store it in a refrigerator at 4°C as a mother liquor. Dilute the prepared DP7-C mother solution to 1mg / ml as the use concentration. Gently mix according to the mass ratio of Scramble siRNA:DP7-C=1:5, and incubate at room temperature for 15 minutes to obtain DP7-C / siRNA complex micelles. Subsequently, gel retardation electrophoresis was used to detect the binding of ScramblesiRNA to DP7-C in different mass ratios. The mass ratios of siRNA and DP7-C were 1:0, 2:1, 1:1, 2:1, 3: 1, 4:1, 5:1, 6:1, 8:1, 10:1.

[0119] The experimental results show that: gel retardation electrophoresis results show that there is no free siRNA band when the mass ratio of siRNA and DP...

Embodiment 2

[0120] Example 2. Preparation and Characterization of DP7-C / siRNA Micelles Encapsulated by Hyaluronic Acid

[0121] 1. Preparation and characterization of hyaluronic acid-coated DP7-C / siRNA micelles

[0122] Weigh 10 mg of hyaluronic acid (HA, average molecular weight 35,000 Daltons) powder, dissolve it in MilliQ water, and store it in a refrigerator at 4°C as a mother liquor. Take the prepared HA mother solution and dilute to 1mg / ml as the use concentration. According to the mass ratio of HA to DP7-C as 1:4, 1:2, 1:1, 1:0.5, 1:0.25, add HA to the DP7-C / siRNA prepared in Example 1 in the aqueous solution, Mix gently, and let stand at room temperature for 10 minutes to obtain HA / DP7-C / siRNA micelles.

[0123] The experimental results show that: using a particle size potentiometer, it is found that when the mass ratio of HA to DP7-C is 1:1, the particle size of HA / DP7-C / siRNA micelles is 105.70±2.12nm, and the Zeta potential is - 24.60±0.37mV ( figure 2 A-B) (the siRNA cont...

Embodiment 3

[0124] Example 3. Stability study of hyaluronic acid-coated DP7-C / siRNA micelles as siRNA carrier

[0125] 1. Long-term storage stability of hyaluronic acid-coated DP7-C / siRNA micelles

[0126] At the 1st, 2nd, 3rd, and 4th week, 1.0 μg siRNA and 5.0 μg DP7-C were mixed gently, incubated at room temperature for 15 minutes, then added 5.0 μg HA, mixed gently, and incubated at room temperature for 10 minutes. The obtained HA / DP7-C / siRNA micelles were stored at 4°C or room temperature. At the fourth week, SDS was added to the above solution, and treated at room temperature for 20 minutes, so that the siRNA wrapped in the micelles became free for detection. 1 μg siRNA was used as the control group, and the results were detected by 1% agarose gel electrophoresis.

[0127] The results show that HA / DP7-C / siRNA can be detected by gel retardation electrophoresis when HA / DP7-C / siRNA is stored at 4 degrees or at room temperature for 1 to 4 weeks, indicating that HA / DP7-C / siRNA has a go...

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Abstract

The invention belongs to the field of biological medicine, and particularly relates to a micelle, a nucleic acid delivery system and a nasal mucosa drug delivery system. The invention aims to solve the technical problems that a traditional glioma treatment mode is poor in effect, other administration means are large in invasiveness, and the blood brain barrier affects drug aggregation in the brain. According to the technical scheme for solving the technical problem, micelle formed by mucopolysaccharide wrapped hydrophobic modified cationic polypeptide is provided as a delivery carrier of nucleic acid, and nasal mucosa administration is facilitated to treat central nervous system diseases. The micelle formed by wrapping the polypeptide with the mucopolysaccharide can efficiently deliver the medicine into cells; especially, the siRNA can be efficiently delivered to the central nervous system through the nasal cavity, gastrointestinal tract degradation and blood brain barrier are avoided, aggregation and treatment effect of the medicine in the brain are enhanced, and the medicine has a good clinical application prospect.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to micelles, a nucleic acid delivery system and a nasal mucosa drug delivery system. Background technique [0002] Nasal drug delivery has been considered as a potentially non-invasive route of drug delivery due to the anatomically unique physiological connection between the nasal and cranial cavities. Compared with other types of administration methods, the advantages of nasal mucosal administration are mainly reflected in: (1) it can avoid gastrointestinal degradation and liver first-pass effect; (2) drugs can bypass the blood-brain barrier and directly accumulate in the brain, Increase the bioavailability of the drug; (3) reduce the systemic exposure of the drug, thereby reducing unnecessary systemic side effects. [0003] RNA interference is a technology that introduces double-stranded RNA homologous to the endogenous mRNA coding region into cells to degrade the target mR...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K31/713A61K47/36A61K47/42A61K47/54A61K47/60A61P25/28A61P35/00
Inventor 杨莉
Owner SICHUAN UNIV
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