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The Drug Delivery System—liposome (part one)

Posté le 18/1/2020 à 06:51 - 0 Commentaires - poster un commentaire - Lien

As a good drug carrier, liposomes have the characteristics of wide range of drug loading, high efficiency and low toxicity, can increase the stability and solubility of the drug contained, and give drug delivery characteristics such as drug targeting and slow release, and can effectively improving the bioavailability of drugs. Liposome has been a hotspot in the field of research. In this article, the construction of liposomes from the results of liposome results, particle size design and screening of preparation methods are discussed. Liposomes are single-layer or multi-layer vesicles with an aqueous phase inside, which are composed of ordered lipid bilayers. They have a bilayer structure similar to biofilms, so they are called artificial biofilms. The main building materials are phospholipids and cholesterol, in which the phospholipid molecule contains a polar phosphate group and two non-polar long hydrocarbon chains, so it is amphiphilic. Under specific conditions, the polar head and polar head of the phospholipid molecules polymerize, and the non-polar tail and non-polar tail polymerize to form a stable bilayer structure. All liposomes can contain water-soluble and lipids, respectively. Soluble drugs have a wide range of drug loading in the phospholipid bilayer and internal water phase. In addition, because liposomes are easily phagocytosed by monocyte phagocytic systems represented by macrophages when they enter the body, liposomes have good passive targeting of organs with developed monocyte phagocytic systems such as the liver and spleen, so it is an ideal drug carrier for treating diseases such as liver parasitic disease, leishmaniasis, leukemia, rheumatoid arthritis. Compared with ordinary preparations, the drug contained in liposomes has the characteristics of slow drug release, which can effectively improve the bioavailability of drugs. In addition, liposomes have strong penetration and retention effects (EPR) in the tumor microenvironment, so they are often used as carriers of antitumor drugs. Based on the above characteristics, liposomes have become hotspots in research and application in many fields. In recent years, the emergence of some new liposomes such as magnetic liposomes, heat-sensitive liposomes, pH-sensitive liposomes, etc. have also attracted people's attention. So far, more than 10 kinds of liposome drugs have been marketed in many countries, such as the antitumor drug doxorubicin liposome (Caelyx?), Vincristine sulfate liposome (Marqibo?), Etc.
  1. Liposomal design
Liposomes can be structurally divided into monolayer liposomes, multilayer liposomes, and polycystic liposomes, where monolayer liposomes include large monolayers and small monolayer liposomes. Affected by the physicochemical properties of drug oil-water partition coefficient, ionoelectricity, etc., different types of drugs and liposome carriers have different minimum rules, so they show different drug loading trends. According to this law of action, corresponding liposome structure, or proper modification of the membrane material and drug structure can effectively improve the encapsulation efficiency of liposomes, increase drug loading and stability. 1.1.1 Drug oil-water partition coefficient and drug loading position The oil-water partition coefficient P is an important physical and chemical property of a drug, and refers to the ratio of the concentration of the drug in the oil phase to the water phase in an equilibrium state. It can be used to predict the solubility and pharmacokinetic characteristics of drugs in vehicles, and provide theoretical basis for dosage form design. Generally, the lgp of fat-soluble drugs is greater than 4.5, and the lgp of water-soluble drugs is less than 0.3. The lgp of amphiphilic substances is between two values. Liposomes are designed to be hydrophilic and lipophilic, which can contain both water-soluble and fat-soluble substances. However, due to the characteristics of the drug and the structure of the liposome, the suitable positions of drugs with different properties are different. Fat-soluble drugs are usually embedded in the phospholipid bilayer membrane, which can achieve a higher encapsulation rate, which can accordingly increase the solubility of hydrophobic drugs and extend the systemic circulation time. Huan Yu et al. constructed ginsenoside Rg3 liposomes, which are hydrophobic anticancer active ingredients of ginseng, using lecithin as the membrane material, with an encapsulation rate of 82.47%. The pharmacokinetic parameters Cmax and AUC were increased to the normal solution group 1.19 and 1.52 times. Other studies have shown that the use of a systematic optimization scheme (DOE) can increase the encapsulation efficiency of the antifungal hydrophobic drug itraconazole to about 90% and greatly increase its solubility. Although water-soluble drugs are easily soluble in the external aqueous phase during the liposome construction process, the volume of the external aqueous phase water and the medium is generally larger than the internal aqueous phase volume. Therefore, a considerable part of the water-soluble drugs are retained in the external aqueous phase. When prepared by the traditional method, the water-soluble drug stays in the external water phase, so when the traditional method is used for preparation, the encapsulation rate of the water-soluble drug is generally not high. Haran et al. found that the encapsulation efficiency of daunorubicin, epirubicin and doxorubicin increased with the increase of oil-water partition coefficient. To be continued in Part Two…

Facts about mesenchymal stem cells

Posté le 16/1/2020 à 14:08 - 0 Commentaires - poster un commentaire - Lien

Bone marrow primitive mesenchymal stem cells are bone marrow stromal stem cells. They are a subpopulation of cells found in mammalian bone marrow stromal cells that have multiple differentiation potentials to form bone, cartilage, fat, nerves and myoblasts. They not only have mechanical support for hematopoietic stem cells (HSC) in the bone marrow, but also secrete a variety of growth factors (such as IL-6, IL-11, LIF, M-CSF, and SCF) to support haemopoiesis. Mesenchymal stem cells (MSCs) are a type of early undifferentiated cells that have the characteristics of self-renewal, self-replication, unlimited proliferation, and multidirectional differentiation. They can secrete cytokines to reduce inflammation, reduce tissue cell apoptosis, and promote proliferate and perform immune regulation of endogenous stem progenitor cells, so as to achieve the effect of repairing tissues and organs. After continuous subculture and cryopreservation, it still has the potential for multi-directional differentiation, which is called "universal cells" in the medical community. Functions of mesenchymal stem cells
  1. Multi-directional differentiation: they have strong proliferation ability and multi-directional differentiation potential;
  2. Immunomodulation: they are low immunogenicity, with immunoregulatory function. They won’t cause immune rejection, and can inhibit rejection;
  3. Rich in quantity: they are rich in various tissues and easy to collect.
  4. Strong fertility: up to 1 billion cells can be cultured in vitro for multiple uses.
  5. Safe and reliable: their genes are stable, not easy to mutate, and still have the characteristics of stem cells after multiple passages.
  6. Awide range of application: they have a wide range of applications and can be used to treat almost all tissue damage, aging and degenerative diseases.
Applications of mesenchymal stem cells in humans
  1. The cells are differentiated into functional cells, replacing functional cells that are in decline or injury;
  2. Start the sequential expression of regeneration-related genes, so that endogenous decline of tissues and organs and damage repair are initiated;
  3. Exogenous cells enter the body, secrete a variety of growth nutrition factors, and improve the internal microenvironment of tissues and organs;
  4. Immunomodulation can reduce the inflammatory response of local tissues and organs;
  5. Activate and improve the quality of immune cells and eliminate and prevent hidden diseases
  6. Differentiate skeletal muscle cells, make fat distribution even, muscles firm, muscles and bones soft;
  7. Promote collagen production, a variety of growth factors secreted by cells, effectively regulate the endocrine system and hormone system.
Diseases available for mesenchymal stem cells ① Hematological diseases: mainly for leukemia; ②Nervous system diseases: such as Parkinson's syndrome, Alzheimer's disease, traumatic brain injury, spinal cord injury, motor neuron disease, etc .; ③ Parenchymal organ damage or disease: such as cirrhosis and its complications, lung and other tissue fibrosis; ④ Immune system diseases: mainly use the immune regulation of stem cells, such as systemic lupus erythematosus, rheumatoid arthritis, etc .; ⑤ Cardiovascular diseases: such as myocardial infarction, vascular disease, ischemic heart disease, etc .; ⑥ Metabolic diseases: such as diabetes and its complications; ⑦ Patellar joint diseases: such as osteoarthritis, femoral head necrosis, etc .; ⑧Reproductive system diseases: such as premature ovarian failure, endocrine disorders, etc. ⑨ Other fields, such as corneal stem cells for eye diseases, stem cell anti-aging, etc. Creative Biolabs can provide phenotypic, genetic, and functional assessments of your MSC population of interest using various techniques and tools. We adapt to your requirements by providing either individual service modules or a fully comprehensive service package.
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