Nano-drug carrier and drug release system

Abstract

The invention provides a nano-drug carrier and a drug release system, the nano-drug carrier comprises a drug loading core and a responsive shell arranged outside the drug loading core, and the drug loading core is loaded with a nano-drug; the surface of the responsive shell is modified with a targeting ligand, and the targeting ligand can specifically target pain-related cells or tissues. According to the nano-drug carrier and the drug release system provided by the invention, precise long-acting treatment of chronic pain is realized through combination of an environment-responsive carrier and an active targeting technology. The technology can significantly improve local accumulation of the medicine and reduce systemic toxicity, and is suitable for management of intractable pains such as neuropathic pains and osteoarthritis.

Description

Technical Field

[0001] This application belongs to the technical field of drug delivery systems and relates to a nano-drug carrier and a drug delivery system. Background Art

[0002] Chronic pain is a long-term pain state that seriously affects the quality of life of patients. Traditional pain management methods, such as oral medications and injections, have problems such as short drug half-lives, many side effects, and poor patient compliance. The application of nanotechnology in the field of drug delivery provides new possibilities for chronic pain management, but its stability, biocompatibility, and long-term release effects still need to be improved. Summary of the Invention

[0003] In view of the above problems, this application provides a nano-drug carrier and a drug delivery system that can stably and long-term release drugs to achieve precise and long-lasting treatment.

[0004] The above-mentioned nano-drug carrier includes a drug-loading core and a responsive shell disposed outside the drug-loading core, and the drug-loading core encapsulates nano-drugs; The surface of the responsive shell is modified with a targeting ligand, and the targeting ligand can specifically target pain-related cells or tissues.

[0005] In one possible implementation manner, for the nano-drug carrier of this application, the drug-loading core is made of one of liposomes, polymer nanoparticles, or metal-organic frameworks.

[0006] In one possible implementation manner, for the nano-drug carrier of this application, the responsive shell includes a pH-sensitive layer, and the pH-sensitive layer degrades at the inflammatory site.

[0007] In one possible implementation manner, for the nano-drug carrier of this application, the responsive shell includes ROS-responsive groups, and the ROS-responsive groups break at the oxidative stress microenvironment.

[0008] In one possible implementation manner, for the nano-drug carrier of this application, the responsive shell includes an enzyme-sensitive coating, and the enzyme-sensitive coating is a pain-related enzyme for targeting.

[0009] In one possible implementation manner, for the nano-drug carrier of this application, the targeting ligand includes a conjugated nerve growth factor antibody, and the conjugated nerve growth factor antibody can enhance the directional delivery to the dorsal root ganglion.

[0010] In one possible implementation, for the nano-drug carrier described in the present application, the targeting ligand includes a CX3CR1 receptor ligand, and the CX3CR1 receptor ligand can enhance the directional delivery to spinal cord glial cells.

[0011] The above drug delivery system includes a micropump, and the above-mentioned any nano-drug carrier is loaded into the micropump. The release rate of the micropump can be controlled by programming to achieve continuous and stable drug release.

[0012] In one possible implementation, for the drug delivery system described in the present application, the drug delivery system is implantable and is implanted into the patient's body through surgery.

[0013] In one possible implementation, for the drug delivery system described in the present application, the drug delivery system is non-implantable and is administered through a skin patch.

[0014] Advantages of the present application: The nano-drug carrier and drug delivery system provided by the present application achieve precise and long-term treatment of chronic pain through the combination of an environmentally responsive carrier and active targeting technology. This technology significantly increases local drug accumulation and reduces systemic toxicity, and is applicable to the management of refractory pain such as neuropathic pain and osteoarthritis. Specific embodiments

[0015] The embodiments of the present application provide a nano-drug carrier, which includes a drug-loading core and a responsive outer shell arranged outside the drug-loading core. The drug-loading core encapsulates nano-drugs; The surface of the responsive outer shell is modified with a targeting ligand, and the targeting ligand can specifically target pain-related cells or tissues, wherein: 1. Nano-carrier structure design The drug-loading core (such as gabapentin, lidocaine or natural analgesic peptides) uses liposome / polymer nanoparticles (PLGA, chitosan) or metal-organic frameworks (MOFs).

[0016] Responsive outer shell: pH-sensitive layer: Degrades at the inflammatory site (pH 6.5 - 7.0) to release the drug.

[0017] ROS-responsive group (such as a thioether bond): Breaks in an oxidative stress microenvironment.

[0018] Enzyme-sensitive coating: Targets pain-related enzymes (such as MMP-9).

[0019] 2. Targeting modification Active targeting ligand: Coupled with nerve growth factor (NGF) antibody or CX3CR1 receptor ligand to enhance the directional delivery to dorsal root ganglion (DRG) or spinal cord glial cells.

[0020] 3. Controlled release mechanism Sustained release: Achieve drug release for more than 72 hours through the degradation kinetics of the carrier.

[0021] Release on demand: Combined with near-infrared light (NIR) or ultrasound triggering for breakthrough pain intervention.

[0022] Technical effects achievable: The local drug concentration is increased by 5 - 10 times, and the systemic exposure is reduced by more than 60%.

[0023] Animal models show that the analgesic effect of a single dose lasts ≥ 7 days (control preparation ≤ 2 days).

[0024] The carrier has good biocompatibility, and the cell survival rate > 90% (CCK-8 method). Examples

[0025] Prepare a nano-drug carrier, select a polymer with high biocompatibility such as poly(lactic-co-glycolic acid) (PLGA) as the carrier material, and encapsulate an analgesic drug such as ibuprofen in it through the emulsification method to form nanoparticles. Then, modify the targeting ligand such as folic acid on the surface of the carrier by covalent bonding or physical adsorption to improve the targeting to pain-related cells. Examples

[0026] Prepare a drug release system, load the above nano-drug carrier into a micropump, and control the release rate of the micropump through programming to achieve continuous and stable drug release. This system can be implantable and implanted into the patient's body through surgery, or non-implantable and administered through a skin patch or other means.

[0027] Through the combination of an environmentally responsive carrier and active targeting technology, achieve precise and long-term treatment of chronic pain. This technology significantly increases local drug accumulation and reduces systemic toxicity, and is applicable to the management of refractory pain such as neuropathic pain and osteoarthritis.

[0028] Finally, it should be noted that: The above embodiments are only used to illustrate the technical solutions of the present application, and are not intended to limit them; although the present application has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: They can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements are all within the protection scope of the present invention.

Claims

1. A nano drug carrier, characterized in that, It includes a drug-loaded core and a responsive shell disposed outside the drug-loaded core, and the drug-loaded core encapsulates nano-drugs; The surface of the responsive shell is modified with a targeting ligand, and the targeting ligand can specifically target pain-related cells or tissues.

2. The nano-drug carrier according to claim 1, characterized in that, The drug-loaded core is made of one of the materials of liposomes, polymer nanoparticles or metal-organic frameworks.

3. The nano drug carrier according to claim 1, characterized in that, The responsive shell includes a pH-sensitive layer, and the pH-sensitive layer degrades at the inflammatory site.

4. The nano-drug carrier according to claim 1, wherein The responsive shell includes ROS-responsive groups, and the ROS-responsive groups break in an oxidative stress microenvironment.

5. The nano-drug carrier according to claim 1, wherein, The responsive shell includes an enzyme-sensitive coating, and the enzyme-sensitive coating is a pain-related enzyme target.

6. The nano drug carrier according to claim 1, characterized in that, The targeting ligand includes a conjugated nerve growth factor antibody, and the conjugated nerve growth factor antibody can enhance the directional delivery to the dorsal root ganglion.

7. The nano-drug carrier according to claim 1, characterized in that, The targeting ligand includes a CX3CR1 receptor ligand, and the CX3CR1 receptor ligand can enhance the directional delivery to spinal cord glial cells.

8. A drug delivery system, characterized in that, It includes a micropump, and the micropump is filled with any one of the nano-drug carriers according to claims 1 to 7. The release rate of the micropump can be controlled by programming to achieve continuous and stable drug release.

9. The drug delivery system according to claim 8, wherein, The drug delivery system is implantable, and the drug delivery system is surgically implanted into the patient's body.

10. The drug delivery system according to claim 8, wherein The drug delivery system is non-implantable, and the drug delivery system is administered through a skin patch.