Rapamycin – only on target
In type 1 diabetes, beta cells of the pancreas cease to function normally due to an attack by their own immune system. As a result, the amount of insulin produced by them decreases, and the patient is forced to receive it from the outside. One of the new potential treatments for diabetes mellitus is the transplantation of donor beta cells, after which the patient will no longer need daily insulin injections. However, scientists are faced with a serious problem: the immune system attacks the transplanted cells and quickly destroys them. Modern immunosuppressive drugs do not sufficiently protect beta cells and have pronounced side effects.
A group of researchers from Northwestern University has described a method that helps to modulate the immune response more effectively. To do this, nanocarriers loaded with the immunosuppressive drug rapamycin were used on immune cells without suppressing the systemic immune response.
Rapamycin has been well studied and is widely used to suppress immune responses during the treatment of autoimmune diseases and after organ or tissue transplantation. Usually, when taken orally, the dosage of rapamycin is carefully controlled to prevent toxic side effects, but at lower doses it has poor efficacy.
The researchers suggested that it is possible to enhance the effect of the drug by placing it in nanoparticles and making sure that it gets into the target tissue.
Immediately after transplantation, their own T cells attack foreign cells and tissues. Immunosuppressants are used to suppress this effect, but they can also weaken the body's ability to fight other infections, as they turn off T cells throughout the body. The researchers placed rapamycin in a polymer nanocarrier made of poly(ethylene glycol)-b-poly(propylene sulfide). Instead of directly affecting T cells, nanoparticles target antigen-presenting cells, providing targeted, controlled immunosuppression.
Subcutaneous administration of nanoparticles with rapamycin allowed to reduce the dose of rapamycin in comparison with oral administration by about half.
To evaluate the effectiveness of the new method, mouse models of type 1 diabetes mellitus were used, which were administered rapamycin orally according to the standard scheme or nanoparticles with rapamycin subcutaneously the day before beta cell transplantation and every three days and for two weeks after. The researchers observed minimal side effects in mice treated with nanoparticles and found that their diabetes was eliminated throughout the 100-day experiment, although treatment should continue throughout the life of the transplant. The team also demonstrated that a population of mice treated with rapamycin nanoparticles had a sustained immune response compared to mice treated with the standard drug treatment.
The researchers have applied for a patent on the technology.
Article by J.A.Burke et al. Subcutaneous nanotherapy repurposes the immunosuppressive mechanism of rapamycin to enhance allogeneic islet graft viability published in the journal Nature Nanotechnology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on materials from Northwestern University: Nanotherapy offers new hope for the treatment of Type 1 diabetes.