Structural composition of 1 liposome
Liposome is actually a term to describe the different arrangements of some compounds with very different chemical and physical properties. And micelles, microemulsions, liquid crystals, monomolecular films, multimolecular films, host-guest systems, etc. They are collectively referred to as "molecular ordered assemblies". Liposomes are spherical with diameters ranging from tens of nanometers to tens of microns. According to the different morphology and structure of liposomes, they can be generally divided into three categories: small single-chamber double-layer liposomes, large single-chamber double-layer liposomes and large multi-chamber liposomes. Single multi-chamber liposomes have different structures, and sometimes spherical, onion-shaped, oval or tubular structures with different sizes appear.
Liposomes as drug carriers
2. Characteristics of1liposome as drug carrier
Liposomes have little toxic and side effects on the body, and their lipid bilayer is very similar to biofilm, which has good histocompatibility and is easily absorbed by tissues. Encapsulation of drugs by liposomes is a physical process, which does not change the molecular structure of drugs. Encapsulating drugs can reduce the toxicity of drugs, reduce the dosage of drugs, and play a role in slow and controlled release. Can wrap drugs of various molecular sizes. Liposomes with special properties, such as immune liposomes and various condition-sensitive liposomes, can be prepared for targeted drug delivery to improve drug efficacy.
2.2 anticancer drug liposomes
Cytotoxic drugs are not selective to normal tissues and pathological parts of the body, so it is difficult to use. The best way is to let the drug directly reach the lesion. Eric and other studies show that the toxicity of liposome encapsulated adriamycin is 50%-70% lower than that of free drugs, and the antitumor activity of liposome dosage form is much higher than that of free drugs. Repeated treatment with adriamycin liposome can increase the survival time of tumor-bearing animals, but it does not prolong the survival time of free drug animals. Many drugs, such as actinomycin D, mitomycin, methotrexate, bleomycin, cisplatin and so on. Liposomes have been wrapped, and the US FDA has approved doxorubicin liposomes TLCD99, amphotericin B and daunorubicin liposomes to enter clinical trials.
2.3 Antiparasitic and Fungal Drug Liposomes
Liposomes can be rapidly absorbed by the reticuloendothelial system after intravenous injection, and some parasitic diseases such as Leishmania and plasmodium enter the human body and parasitize on the reticuloendothelial system. So drugs can be encapsulated in liposomes. When treated with pentavalent antimony, the drug is very toxic, and its therapeutic dose is equal to the toxic dose. After being wrapped with liposome, it is safe and effective to treat experimental Leishmania, and the therapeutic dose is greatly reduced. Das used fucose-fructose receptors on the surface of macrophages to synthesize fucose-containing liposomes, encapsulated antimony compounds and treated hamsters infected with Leishmania for 30 days. The results showed that the effect of drug encapsulated in liposome was enhanced (inhibition rate was 55%), and the effect of liposome containing fucose was more obvious (inhibition rate was 72%), while the inhibition rate of drug without liposome was only 26%.
2.4 Liposomes of peptides and enzymes
Polypeptides and enzyme drugs are biological macromolecules, which are unstable in organisms and easily degraded by proteolytic enzymes, so they have a short half-life in organisms and are mostly not suitable for oral administration. Superoxide dismutase (SOD) can remove excessive superoxide anion free radical damage in the body, and Anderson is easily destroyed by protease hydrolysis. The half-life of liposome in vivo is obviously improved, and liposome can increase the ability of cells to absorb SOD, thus better protecting cells from free radical damage. Amderson and other studies show that the half-life of subcutaneous injection of free IL-2 is only 6min, while that of liposome-encapsulated IL-2 is 68min, and the distribution and pharmacokinetics of liposome-encapsulated IL-2 change greatly. The bioavailability of insulin is low due to the destruction of enzymes and acids in the stomach after oral administration, but these shortcomings can be overcome by encapsulating liposomes, and the blood sugar of animals decreases obviously after oral administration.
Liposomes as vaccine carriers
Allison et al. first reported the immunoadjuvant effect of liposomes in 1974. IIUNA (1995) wrapped influenza virus H3N2 with MDP liposome. After immunizing mice, the number of spleen cells in mice decreased obviously, and the virus titer in mice's lungs shifted, indicating that MDP liposome vaccine can protect mice from influenza virus attack by enhancing cellular immunity. Childers et al. made Streptococcus mutans glucosyltransferase (GTF) liposome into enteric-coated capsules, and gave it to 7 healthy adults orally, 500ug each day, for 3 days, and then fortified 1 time after 28 days. Results The levels of IgA 65, IgA 438+0 and IgA2 in parotid gland secretion of five people increased, reaching the peak on the 35th day, which indicated that liposome vaccine could induce the body to produce secretory GUIgA antibody after oral administration. Liposomes as vaccine adjuvants can enhance humoral immunity and cellular immunity.
Liposomes for immunodiagnosis
Fluorescent substances (such as carboxyfluorescein) or enzyme active substances (such as alkaline phosphatase) are wrapped in liposomes, and then specific antibodies are attached to liposomes. When the antibody on the liposome binds to a specific antigen, the liposome breaks and releases fluorescein, and the antigen content can be determined by measuring its fluorescence intensity. Alkaline phosphatase (AP) is encapsulated in immunoliposomes, and the enzyme substrate is outside the liposomes. When the immunoliposome binds to antigen, the membrane permeability of liposome changes, releasing AP, and AP reacts with substrate to develop color. This method can be used for qualitative or quantitative analysis, and the operation is fast and simple. This method has been used to diagnose lupus erythematosus, syphilis, hepatitis B and mononucleosis. And detecting drugs such as C- reactive protein, immunoglobulin and hormone.
Liposome 5 is used as DNA carrier in gene therapy and nucleic acid immunization.
As an alternative gene carrier, liposome has the characteristics of non-toxicity, non-immunogenicity and biodegradability, which can protect plasmid DNA from being degraded by nuclease and deliver target gene DNA to target cells specifically. Nabel treated 5 melanoma patients with HLA-B7 gene and DC-chol/DOPE cationic liposome complex, injected with different doses of DNA- liposome complex three times, and detected the expression of HLA-B7 protein in tumor tissues of 5 patients by immunochemistry. Among them, 1 patient was treated twice at intervals, and both injected nodules and distant nodules subsided. Will Yoshihisa? Galactosidase cationic liposomes were injected into nude mice bearing ASPC- 1 tumor, and the transfection activity was determined on the third day. The expression of galactosidase in tumor tissue is higher than that in normal tissue. At present, there are 12 gene delivery systems mediated by cationic liposomes in the gene therapy scheme implemented in the United States.
Robinson et al. injected plasmid DNA expressing the protective antigen HA gene of avian influenza virus (AIV) into mice and chickens in 1993, which can produce effective immune protection response against lethal AIV attack. Klavinskis inoculated a single dose of luciferase gene and cationic liposome (DMRIE/DOPE) into nasal mucosa. After 4 weeks, IgA and IgG can be detected in serum. However, after inoculation with naked DNA, only a few antibodies existed, and its luciferase activity increased by nearly 30 times. Luciferase gene DNA liposome complex can cause specific CTL reaction. Norman et al. combined 13 ugcat reporter gene DNA with cationic liposome GAP-DLRIE, and inoculated BALB/c mice with plasmid DNA liposome complex and naked DNA nasal mucosa. The results showed that the expression of cat protein was 0.02ng/mg and that of liposome DNA was 0.02ng/mg after 2 days of inoculation of naked DNA, indicating that the expression of liposome DNA was 45 times that of naked DNA.