CN-121987806-A - Application of mesenchymal stem cell exosome-itaconic acid drug-loading system in preparation of drug delivery for treating retinal artery occlusion nasal cavity

Abstract

The invention discloses application of a mesenchymal stem cell exosome-itaconic acid drug-loading system in a nasal administration preparation for treating retinal artery occlusion, and belongs to the technical field of biological medicines. The drug delivery system comprises a mesenchymal stem cell exosome and itaconic acid or an itaconic acid derivative, wherein the itaconic acid or the itaconic acid derivative is encapsulated in the mesenchymal stem cell exosome. The invention realizes the synergy and superposition of dual effectiveness of exosomes and effective compounds, and the drug carrying system can effectively reduce the damage of retinal structures and visual functions in Retinal Artery Occlusion (RAO) by using nasal administration, simultaneously effectively realize noninvasive rapid drug administration, shorten the clinical RAO administration time and provide time guarantee for good disease prognosis.

Inventors

• XIAO XUAN
• WU MINZE
• ZHOU BING
• FENG JIAQING
• LI YING
• WANG YAQI
• CHEN TING
• CHEN DUAN
• HU LIANG
• XIE HAO
• WANG CHUANSEN

Assignees

• 武汉大学人民医院（湖北省人民医院）

Dates

Publication Date

20260508

Application Date

20260206

Claims (10)

1. 1. A mesenchymal stem cell exosome-itaconic acid drug-loading system is characterized by comprising a mesenchymal stem cell exosome and itaconic acid or an itaconic acid derivative, wherein the itaconic acid or the itaconic acid derivative is encapsulated in the mesenchymal stem cell exosome.
2. 2. The drug delivery system of claim 1, further comprising an additional active ingredient having therapeutic effect on retinal artery occlusion, wherein the active ingredient is encapsulated in mesenchymal stem cell exosomes with itaconic acid or an itaconic acid derivative.
3. 3. The drug delivery system of claim 1, wherein: the mesenchymal stem cells comprise umbilical cord, bone marrow, fat or placenta-derived mesenchymal stem cells; and/or the itaconic acid derivative comprises 4-octyl itaconic acid and dimethyl itaconate.
4. 4. The method for preparing the drug delivery system according to any one of claims 1 to 3, which is characterized by comprising the steps of uniformly mixing mesenchymal stem cell exosomes with itaconic acid or derivatives thereof in a buffer solution, and actively loading drugs by ultrasound to obtain the drug delivery system.
5. 5. A composition comprising the drug delivery system of any one of claims 1-3.
6. 6. Use of a drug delivery system according to any one of claims 1-3 or a composition according to claim 5 for the manufacture of a medicament for the treatment of retinal artery occlusion lesions.
7. 7. The method according to claim 6, wherein the medicine for treating retinal artery occlusion injury comprises any one or more of medicine for preventing and treating retinal ganglion cell injury or death, medicine for promoting retinal microglial cell activation or polarization of microglial cells to M2 type.
8. 8. The method according to claim 6 or 7, wherein the administration of the medicament for treating retinal artery occlusion injury comprises nasal administration, intraocular administration, intravenous injection.
9. 9. The method according to claim 6 or 7, wherein the medicament for treating retinal artery occlusion injury comprises a drop, a spray, a powder, a gel, a microsphere, an emulsion, or an injection.
10. 10. A medicament for treating retinal artery occlusion injury, comprising the drug delivery system of any one of claims 1-3 or the composition of claim 5.

Description

Application of mesenchymal stem cell exosome-itaconic acid drug-loading system in preparation of drug delivery for treating retinal artery occlusion nasal cavity Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a human mesenchymal stem cell exosome-itaconic acid medicine carrying system, preparation thereof and application thereof in treating retinal artery occlusion. Background Retinal Artery Occlusion (RAO) is a critical ophthalmic disorder, and its pathogenic principle is mainly that sudden occlusion of the retinal artery leads to acute dysfunction of retinal tissue, causing serious vision impairment and even blindness. Typical clinical manifestations are sudden, painless vision loss, which typically results in retinal ischemic injury and irreversible death of retinal ganglion cells (retinal ganglion cells, RGCs) within 90 minutes. The main cause of significant vision loss and severe visual field impairment from RAO is death of neuronal RGCs from the inner retina, losing the function of signaling from primary neurons such as photoreceptor cells to the cerebral cortex. The current clinical RAO treatment mainly comprises two aspects, namely 1) treatment aiming at central retinal obstructive embolus, wherein the treatment aims at improving and recovering retinal circulation, the treatment means comprise anterior chamber puncture, acetylglucosamine treatment, eyeball massage, arteriovenous medicament or interventional operation thrombolysis treatment and the like, and 2) protection treatment aiming at retinal ganglion cells, wherein the aim is to protect cells and tissues damaged by retinal ischemia after blood flow recanalization, and the main treatment medicaments comprise mecobalamin tablets, citicoline sodium capsules, nerve growth factor injection and the like. However, the time window for RAO treatment is short (only 90 minutes), and it is reported that only 20% of patients receive limited recovery after vision retreatment, regardless of the type of treatment. Therefore, searching for effective therapeutic drugs of RAO and timely taking the drugs within a treatment window period is a serious problem to be solved in the current clinical RAO treatment. Mesenchymal stem cell exosomes (MESENCHYMAL STEM CELLS-derived exosomes, MSC-Exo) are membrane vesicles released outside cells after fusion of intracellular multivesicles with cell membranes, and are carriers for intercellular signal transmission. MSC-Exo has been demonstrated to also have tissue repair and regeneration functions as an important active substance in paracrine, and "cell-free" therapies based on MSC-Exo exosomes have good application prospects in the fields of tissue repair and regeneration medicine. Itaconic acid (Itaconate, ITA) is an important metabolite in the tricarboxylic acid cycle synthesized by immune cells under inflammatory stimuli, and has the functions of immunomodulation, anti-inflammation, antioxidation, antibiosis, anti-tumor and the like. Itaconic acid itself is highly polar and not easily permeable to cell membranes, limiting its direct application and depending on derivatives to improve permeability, but itaconic acid derivatives such as 4-octyl itaconic acid (4-OI) may be metabolized to pro-compounds in cells, affecting its function. Based on the above, the therapeutic effect of itaconic acid in the current animal experimental study mainly depends on multiple intraperitoneal administration to achieve the effect, but the multiple intraperitoneal injection administration brings challenges to the safety of drug treatment. Therefore, an effective itaconic acid drug carrying system is developed, a safe and rapid drug administration way is searched, and drug treatment is carried out in the onset window period of RAO, so that the method is a new direction of the current RAO treatment. And the mesenchymal stem cell exosome provides an effective carrier for constructing the system. At present, related reports of loading itaconic acid on mesenchymal stem cell exosomes are not seen, and nasal administration of the mesenchymal stem cell exosomes-itaconic acid drug loading system at the same time is also blank in the field, so that the technical bottleneck needs to be solved. Disclosure of Invention The invention aims at solving the technical problem of medicine deficiency in the existing clinical treatment of Retinal Artery Occlusion (RAO), provides a mesenchymal stem cell exosome-itaconic acid medicine carrying system, and a preparation method and application thereof, and particularly relates to application of a noninvasive nasal drop preparation prepared by the medicine carrying system to the protection of retinal structures, functions and retinal ganglion cells in retinal artery occlusion. The mesenchymal stem cell exosome-itaconic acid medicine carrying system has high itaconic acid entrapment efficiency and simple preparation method, and realizes the synergy and su