CN-120859972-B - Stem cell loaded drug-loaded nano vesicle-sericin base hydrogel and application thereof

Abstract

The invention relates to the technical field of medicines, in particular to a drug-loaded nano vesicle-sericin base hydrogel loaded with stem cells and application thereof. According to the invention, sericin is taken as a base material, photo-crosslinking sericin (SerMA) is obtained by chemically grafting sericin (sericin) with methacrylic anhydride, and then acrylic ester-polyethylene glycol-succinimidyl ester (AC-PEG-NHS) modified cell membrane nano vesicles loaded with Procyanidine (PC) are grafted onto a molecular skeleton thereof through photo-crosslinking reaction, so that SerMA-PC@PNVs hydrogel is successfully prepared. In-vitro and in-vivo experimental researches of the hydrogel show that SerMA-PC@PNVs/PDLSCs hydrogel can regulate the polarization state of microglial cells through antioxidation, so that survival of damaged Retinal Ganglion Cells (RGCs) is promoted, and the hydrogel can be used for treating eye diseases such as glaucoma.

Inventors

• ZHU WENXIANG
• DUAN XUANCHU
• XIA MINGFANG
• HUANG WEI
• HUANG QIULING
• ZHOU XIAOYU

Assignees

• 爱尔眼科医院集团股份有限公司长沙爱尔眼科医院

Dates

Publication Date

20260512

Application Date

20250730

Claims (5)

1. 1. The hydrogel composition is characterized in that the hydrogel composition is prepared by methylacryloylation modified sericin and drug-loaded nano vesicles through 405nm light irradiation in the presence of a photoinitiator; The drug-loaded nano-vesicles comprise AC-PEG-NHS modified cell membrane vesicles and glaucoma treatment drugs; The mass ratio of the AC-PEG-NHS modified cell membrane vesicle to the glaucoma treatment drug is 1:2-2:1; The glaucoma treatment drug is procyanidine; the cell membrane vesicles in the AC-PEG-NHS modified cell membrane vesicles are derived from human periodontal ligament stem cells; The AC-PEG-NHS modified cell membrane vesicle is obtained by modifying a cell membrane vesicle by AC-PEG-NHS; the photoinitiator is LAP.
2. 2. The hydrogel composition of claim 1, wherein the concentration of the glaucoma treatment drug is 50 μg/mL to 800 μg/mL.
3. 3. A mixture comprising stem cells, characterized in that it is prepared from stem cells, the methacryloyl modified sericin in the hydrogel composition of claim 1 or 2 and drug-loaded nanovesicles by irradiation with light of 405nm in the presence of a photoinitiator; The photoinitiator is LAP; the stem cells are human periodontal ligament stem cells.
4. 4. Application of at least one of the following I) to II) in preparing products for treating and/or preventing eye diseases: I) The hydrogel composition of claim 1 or 2; II), the mixture of claim 3; The eye disease is glaucoma.
5. 5. The product for treating and/or preventing the eye diseases is characterized by comprising at least one of the following components i) to ii): i) The hydrogel composition of claim 1 or 2; ii) the mixture of claim 3; The eye disease is glaucoma.

Description

Stem cell loaded drug-loaded nano vesicle-sericin base hydrogel and application thereof Technical Field The invention relates to the technical field of medicines, in particular to a drug-loaded nano vesicle-sericin base hydrogel loaded with stem cells and application thereof. Background Glaucoma is a neurodegenerative disease characterized primarily by damage to retinal ganglion cells (Retinal ganglion cells, RGCs). The main treatment of glaucoma is lowering intraocular pressure (Intraocular pressure, IOP) by drugs, laser or surgery, etc. However, these methods only delay disease progression and are not effective in preventing the progressive death and sustained loss of visual function of RGCs, which is also the root cause of blindness from glaucoma. RGCs are terminally differentiated cells that have very poor regeneration capacity and are not self-renewing especially in the adult organism. Apoptosis of RGCs is a challenge for a variety of diseases such as glaucoma, diabetic retinopathy, optic neuritis, and the like. Among these, inflammation is one of the key factors responsible for apoptosis of RGCs. The inflammatory response at the site of injury can lead to excessive accumulation of Reactive Oxygen Species (ROS), which act synergistically with pro-inflammatory cytokines to exacerbate the retinal inflammatory response, further resulting in RCCs injury, damaging the optic nerve. Thus, developing new strategies that can inhibit inflammation and scavenge ROS, thereby promoting survival of RGCs, is a hotspot and a difficult problem for research. In recent years, stem cell transplantation has provided a new solution for the treatment of glaucoma because it can repair or replace damaged RGCs. However, the current approach for intraocular stem cell transplantation is mainly via intravitreal or subretinal injection. The intravitreal injection has the problems of poor cell homing ability, easy cell loss, low survival rate and the like, and the subretinal injection has potential risks of retinal detachment, subsequent neuron injury and the like. Therefore, the development of a novel stem cell transplantation system has important clinical application significance. Disclosure of Invention In view of the above, the technical problem to be solved by the present invention is to provide a drug-loaded nano vesicle-sericin based hydrogel loaded with stem cells and application thereof. The invention provides a drug-loaded nano vesicle, which comprises an AC-PEG-NHS modified cell membrane vesicle and a glaucoma therapeutic drug; The drug-loaded nano vesicle is specifically prepared by mixing an AC-PEG-NHS modified cell membrane vesicle obtained by modifying a cell membrane vesicle through AC-PEG-NHS with an eye disease treatment drug (in the specific embodiment of the invention, the modified cell membrane vesicle is named PNVs, the modified cell membrane vesicle is mixed with the eye disease treatment drug to obtain PC@PNVs), and the mixing step is that porous membranes sequentially at 800nm, 400nm, 200nm and 100nm are repeatedly extruded after ultrasonic treatment at 0-4 ℃. The cell membrane is derived from human periodontal ligament stem cells; The mass ratio of the product to the eye disease treatment drug is 1:2-2:1. According to the drug-loaded nano vesicle, the mass ratio of the product to the eye disease therapeutic drug is optimized to be 1:2-2:1, and the test result shows that the physical stability is the best when the mass ratio of the product to the eye disease therapeutic drug is 1:1. Further, in the invention, the eye disease treatment drug comprises a glaucoma treatment drug, wherein the glaucoma treatment drug comprises procyanidine, cowberry anthocyanin, ginkgo leaf extract, lutein, zeaxanthin, methylcobalamin and/or nicotinamide; In the drug-loaded nano vesicle, the concentration of the glaucoma treatment drug is 50-800 mug/mL. In the invention, the concentration of the glaucoma treatment drug is optimized (the mass ratio of the product to the eye disease treatment drug is always kept to be 1:1), and the result shows that in the hydrogel (the hydrogel contains PC@PNVs and methacryloyl modified sericin SerMA), the compressive strength is firstly increased but is subsequently reduced along with the increase of the content of the PC@PNVs, and when the content of the PC is 400 mug/mL, the SerMA-PC@PNVs have the optimal compressive mechanical property and no cytotoxicity. Further, the cell membrane in the AC-PEG-NHS modified cell membrane vesicle is derived from human periodontal ligament stem cells; The AC-PEG-NHS modified cell membrane vesicle is obtained by modifying a cell membrane vesicle by AC-PEG-NHS. The mass ratio of the cell membrane vesicle to the AC-PEG-NHS is 1:2; the photoinitiator comprises LAP and/or Irgacure 2959, and in a specific embodiment of the invention, the photoinitiator LAP is 0.5 weight percent. In a specific embodiment of the present invention, the preparation method of the drug-load