Technological Developments

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Rafarma Pharmaceuticals is interested in developing and bringing to market some new technological platforms and creating a scientific basis for working with them:

 

• Microspheres and preparations based on them

Nanostructured microspheres based on an alloy of silicon and phosphorus, which are being developed by Bebig LLC, are suitable for primary and metastatic unresectable liver cancer and pancreatic cancer treatment. Polymeric microspheres creation and microspheres based on amorphous silicon compounds (special glasses) will make it possible to obtain an effective cancer treatment method that ensures minimal damage to healthy tissue.

 

• Radiopharmaceuticals with "α" and "β" emitters

Radiopharmaceuticals, in which, due to the high energy of sequential decay, a radioactive ion can kill tumor cells, are the most promising method of treating cancer today. The medicines provide the most localized radioactive effect and practically do not irradiate adjacent tissues. Radiopharmaceuticals with "α" and "β" emitters demonstrate sufficient stability and efficacy during clinical trials, so there are high expectations for them.

 

• Mycrobiota preparations

The microbiota plays a significant role in the human body, so microbiome modulator pharmaceuticals and specially engineered symbiont bacteria are a promising treatment for many diseases. The principle of an innovative treatment method is based on the colonization of metabolically active bacteria in therapeutically accessible loci of the body, which leads to functional changes in the microbiome, organ function and immunity.

 

• Technologies for the therapeutic use of exosomes

Rafarma Pharmaceuticals aims to develop an advanced technology platform for exosome therapy that will enable the cosmetic anti-aging drugs creation and therapeutics for neurodegenerative and immune disorders treatment.

 

What are exosomes?

Exosomes are elements of extracellular transport originating from early endosomes. Exosomes can carry various components of the donor cell, including proteins, lipids, mRNA, microRNAs, small interfering RNAs (miRNAs), and DNA. Exosomes are secreted by almost all cells in the body. They are involved in the biosignaling and transport of active molecules between cells.

 

Exosomes are formed inside the cell by the cytoplasmic membrane invagination while accumulating active molecules. Then these structures called early endosomes mature to release into the extracellular space. Specific proteins on the surface of the exosomes provide targeting specific cells for signal transduction or active molecules delivery.

 

The Therapeutic Potential of Exosomes

Artificially engineered and isolated exosomes can be brought into play for novel high-tech drugs development. Regardless of origin, all exosomes have annexins on their surface, Rab proteins, Alix proteins, and other proteins which regulate the processes of biogenesis, the fusion of the mature exosome membrane with the membrane of the recipient cell, and signal transduction. Heat shock proteins, which role is to control and normalize protein structure, are also an obligate internal component of all exosomes. Exosomes can transport various mediators, including cytokines (IL-1β, IL-1α, TNF, IL-6, VEGF, etc.) and chemokines (IL-8, CX3CL1, etc.).  These features of exosomes indicate their potential for a therapeutic purposes’ variety, such as target drug delivery and synthesis of prophylaxis medications. 

 

Currently, several strategies of exosomes loading exist. Exosomes could engineer to carry proteins, nucleic acids, or small active molecules. Exosomes with payload can isolate in several ways, including differential centrifugation, filtration, size-exclusion chromatography, and polymer precipitation. Isolated exosomes characterize high bioavailability and low-to-zero toxicity.

 

Our Exosomes Projects

1. Exosome-based medicine for the atherosclerosis prevention. An atherosclerotic lesion is a local inflammation triggered and propagated by mediators produced by macrophages and T-cells. Other types of immune cells, including dendritic cells, natural killer cells, and innate lymphoid cells are also involved in the pathogenesis of atherosclerosis. LDL (low-density lipoproteins) accumulated in the arterial wall is the principal antigen in atherosclerosis. Activation of antigen-specific Th-1 cells promotes plaque inflammation. Animal studies have shown that several cytokines could protect arterial walls from atherosclerosis, while others contribute to the disease progression. Immunization of the experimental animals in a model of hypercholesterolemia with oxidized LDL particles unexpectedly led to the activation of atheroprotective immunity involving regulatory T-cells and reduction of arterial wall damage. These observations suggest that new exosome-based therapeutic approaches can selectively modulate an atheroprotective immune response.

2. Topical and systemic anti-aging exosome-based drugs. We study the senescent cells’ apoptosis acceleration by inhibiting the GLS1 glutaminase. Research articles indicated that the glutamate metabolic enzyme GLS1so inhibitor could selectively eliminate aging cells in vivo in various organs and tissues of aged mice, improving age-related tissue dysfunction and symptoms of obesity, diabetes, atherosclerosis, and non-alcoholic steatohepatitis. Age-related changes were reduced in the kidneys and blood vessels, while inflammation and glucose metabolism markers were improved when disabling this enzyme. Further GLS1 inhibitor therapeutic potential study will lead to significant progress in the anti-ageing exosome-based drugs development.

3. Exosome-based drugs for neurodegenerative diseases. Research groups led by Ashok K. Shetty and Darwin J. Prockop (Texas A&M College of Medicine) demonstrated that intranasal administration of mesenchymal stem cell-derived exosomes reduces the severity of brain damage associated with status epilepticus. Based on these data we assume the therapeutic potential of exosome-based drugs for neurodegenerative diseases with similar pathogenetic mechanisms in the advanced stages, including Alzheimer's disease, parkinsonism, and multiple sclerosis.

 

• Drugs for the treatment of diseases without effective therapeutic methods

According to Rafarma Pharmaceuticals' opinion, one of the most promising products for development is Hashimoto's consequence disease treatment drug. Although a significant number of problems with the health and appearance of patients accompanying this thyroid disease, there is no specific therapy for it.

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