Research on carriers of peptide & protein drugs
Peptides and proteins are widely found in living organisms. Has a variety of physiological and biochemical functions. It is also a large class of biochemical substances with medicinal value.
Cell growth factor (cytokine) is a general term for small molecule proteins secreted by cells with biological regulatory functions. In many cases. The interaction between various immune cells is mediated by cytokines. It can promote or inhibit cell proliferation, differentiation, migration and gene expression. It has a large number of applications in tissue engineering and the treatment of diseases. The academic community currently classifies cell growth factors into the category of polypeptides.
Characteristics of peptide and protein drugs
In the process of basic research and clinical use. It has been found that polypeptide and protein drugs have the following characteristics: high biological activity. Physiological effect is strong. Due to the characteristics of the protein's own structure, peptides and protein drugs are prone to hydrolysis, denaturation, aggregation or precipitation and other changes. As a result, the potency is reduced or the effect is completely lost; hydrocolloids can be formed; the half-life in vivo is short,high clearance rate. Proteins are easily destroyed by enzymes, bacteria and body fluids in the body; low bioavailability by non-injection administration; expensive; immunogenic; can be used as a carrier for other drugs.
Requirements for carrier materials for peptide and protein drugs
Because peptides and protein drugs have the characteristics of poor stability, short half-life in vivo, and easy to be degraded, peptides and proteins have the following corresponding requirements for their carriers:
1.No damage or inhibition to normal cells and tissues.
2.It is targeted. Most polypeptides and proteins have no targeting properties, so they can only find a way to do it on a carrier, such as a liposome as a carrier.
3. Biodegradable or metabolized into non-toxic substances, and excreted.
4. It can increase the physical and chemical stability of the drug. Protein and polypeptide drugs themselves have poor stability. Therefore, it is greatly restricted in use. Some carriers can increase the physical and chemical stability of the drug; improve the transport process of the drug in the body and prolong the action time of the drug; it can change the route of administration, and most of the pure polypeptide and protein drugs can only be administered by intravenous injection.
In recent years, changing the route of administration of polypeptide and protein drugs has become a research hotspot, such as aerosol inhalation administration, oral administration, and transdermal administration.
Types and properties of carrier materials for peptide and protein drugs
At present, more and more protein and polypeptide drugs are synthesized with the help of recombinant DNA technology and custom peptide synthesis. These recombinant proteins are chemical copies of natural polypeptides and proteins, and have almost identical physiological, biochemical functions and pharmacological characteristics. Although a small dose of recombinant protein showed great physiological activity in animal experiments. But many drugs are not yet available for clinical use. If administered orally, these polypeptides and proteins are rapidly degraded by proteolytic enzymes in the gastrointestinal tract. If injected intravenously or intramuscularly. Due to its short biological half-life. Patients often require repeated dosing, which is difficult for patients to accept and risk of infection
The commonly used carrier materials for peptide and protein drugs are as follows:
1. Collagen
It has a wide range of sources, is easy to extract and purify, is easy to shape, can be degraded, and is non-toxic to the body. good biocompatibility. However, there are disadvantages of high cost and easy degradation.
2. Gelatin
It is a polymer formed by cross-linking of amino acids and peptides. It is biodegradable. Almost non-immunogenic. Gelatin is easy to form a network structure and is relatively stable at room temperature and dry state. Can be left for several years. It is thermally reversible and melts when heated. solidifies on cooling
3. Calcium phosphate bone cements (calcium phorphate bone cements, CPBC8)
After curing, a microporous structure is formed. And it can be degraded in the body.
4. Polysaccharides
is a monosaccharide polymer. It has the characteristics of stable nature, safe and non-toxic, easy to form and biodegradable. Commonly used polysaccharide carrier materials include chitosan, pectin, starch, dextran and the like. Among them, the most widely used are chitosan, pectin, starch, glucan and so on. One of the most widely used is chitosan
5. Combination of nanotechnology and carrier
Use natural or synthetic polymers as carriers for controlled drug release. Prepared into spherical or sac-like particles with a diameter of nanometers. A container-type system that uses polymer materials as capsule membranes and wraps solid or liquid drugs as capsules is called microcapsules. The medium system in the form of microspheres is called microspheres. The materials for preparing nano-microspheres need to have the characteristics of biocompatibility, biodegradability, orientation, controllability, intelligence, cell permeability and good drug-carrying capacity. The most commonly used materials are polylactic acid. Nano-microspheres are absorbed by organs or tissues, which can significantly prolong the efficacy and improve the availability. Through the regulation of the encapsulation material, the sustained release and targeted distribution of the nanospheres in vivo can be achieved.
At present, there are many methods for slow release of cytokines using carrier systems. The best method is to use nanotechnology and carrier technology to prolong the efficacy of cell growth factors, which has broad prospects. Some of them have been applied clinically.
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