hello virag thank you for the valuable comment I hope i can give you satisfactory answer. Let us see the general method of preparing liposomes. 1. Powdered lipids+ lipid soluble drug are added to organic solvent in RBF 2. It is subjected freeze drying process --> formation of lipid cake 3. Aqueous soln+water soluble drug is added to the lipid cake 4. Hydration and Agitation process 5. Formation of large multilamellar vesicles LMVs 6. LMVs---> Sonication & Homogenization---> formation of small unilamellar vesicles Step 4 may increase the temperature of the formulation as you said. So severe agitation should be prevented. Also the Sonication process causes degradation of lipid core and other soluble ingredients in the formulation. This is now replaced with French press where high pressures are applied. The disadvantage in this is its very costly equipment. When the temperature exceeds 42/46oC or 113oF the lipid core dissolves and releases the drug-->Thermosensitive liposomes. In this case, the process should be selected carefully While for the preparation of normal liposomes other methods can be applied viz. Mechanical agitation Solvent dispersion Detergent solubilization etc Ref.: http://www.authorstream.com/Presentation/vsnmurthy-331492-liposomes-ppt-...

dear abhishek thank you for the valuable comment. Coming to your query the relation between pH and temperature is the same which we study in ceutics. As temperature increases--> viscosity decreases-->mobility of ions increases Other side is increase in temperature -->causes dissociation of ions (especially for weak acids and bases). Since pH is -log[H+], it deviates. So generally when we mention temperature the pH should also be read. for eg. temp 22oC ,2.05 pH. The pH is adjusted using suitable buffers so that it shows minimal deviations when hyperthermia is applied. Ref.: http://www.reagecon.com/techpapers/effectsoftemperatureonphv4.pdf

ketan thank you for the valuable comment.. Well, Thermosensitve liposomes are used for targeted delivery of chemotherapeutic drugs. The research is mostly carried out in the cancer area because of their systemic action rather than the required local action.

hello sailesh thank you for the valuable comment. Coming to your queries The temperature range is usually from 42-46oC or 113oF app Thermosensitive liposomes are designed in such a way that they release the drug upon local heating. Hence the name "thermosensitive". When the temperature crosses the above range the lipid core dissolves-->bursting of the drug Well, these liposomes first reach the systemic circulation. Due to hyperthermia (heating a particular tumor portion) causes increase in the pore size of blood vessels--> permeation of thermosensitive liposomes-->dissolution of lipid core-->preferential targeting Ref.: http://www.cancer.gov/cancertopics/factsheet/Therapy/hyperthermia

thank you madam for your encouraging comment

hi anil thank you for the valuable comment. the phospholipid layer here indicates the liposomal layers. Liposomes in systemic circulation--> high temperatures at tumor portions--> dissolution of outer layer of liposomes--> availability of drug. You can find furthur information regarding hyperthermia and its applications in the posted references.

Let us see how the machine works. Due to the application of ultrasound vibrations, the tissue cells move rapidly which results in friction between them causing rise in temperature. Just like rubbing our hands--> mild heat is generated. We can draw general limitations here ~ Skilled personnel is required ~ Excess heat may lead to boils or burns in the area ~ Finally, common to any equipment - its cost.

hello shafi.. thank you for the valuable comment. Preparation of liposomes is done in following steps: 1. Powdered lipids+ lipid soluble drug are added to organic solvent in RBF 2. It is subjected freeze drying process --> formation of lipid cake 3. Aqueous soln+water soluble drug is added to the lipid cake 4. Hydration and Agitation process 5. Formation of large multilamellar vesicles LMVs 6. LMVs---> Sonication & Homogenization---> formation of small unilamellar vesicles Liposomes are phospholipid molecules that are capable of encapsulating active drugs (antibiotics,antineoplastics). Stealth liposomes containing doxorubicin(DOXIL) are done with surface coating of Methoxypolyethyleneglycol (MPEG). Intratumoral distribution of DOXIL: DOXIL - Doxorubicin HCl is an antineoplastic. Features: ~ Has rapid rate of penetration ~ Inhibits mitotic division ~ Has rapid chromatin binding ~ Inhibits nucleic acid synthesis ~ Causes mutagenesis and chromosomal aberrations Main side effect is MYELOSUPPRESSION. Coming to intratumoral distribution, DOXIL is tested in normal and Kaposi sarcoma affected patients. 20 mg/m2 Doxil(r) is injected in both categories. Biopsies were collected from KS and normal lesions at 48 and 96hrs respectively. The concentration of Doxil(r) was found to be more in KS lesions than in normal at 48hrs posttreatment. Thus more drug is delivered to the tumor patients than normal ones. Reference : http://www.kodc.or.kr/cmed/down/DOXIL_PI.pdf

hello sandeep thank you for the valuable comment. Well, coming to the applications, liposomes in combination with hyperthermia are used to treat cancers affecting oesophagus, sarcoma, ovaries, Kaposi sarcoma. However metastases needs whole body hyperthermia. This has some serious side effects. Coming to the materials, MPPC, 1-palmitoyl-2-hydroxy-snglycero-3-phosphocholine; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; HSPC, hydrogenated soy sn-glycero-3-phosphocholine; ---> liposome layer formation DSPE-PEG-2000, 1,2-distearoyl-snglycero-3-phosphoethanolamine-N-polyethylene glycol 2000--> ensures higher life span in circulation. Reference: http://cancerres.aacrjournals.org/content/60/5/1197.full.pdf+html Cancers can also be treated using magnetic liposomes along with hyperthermia. You can find more information in MAGNETIC TARGETED CARRIERS - TARGETED DRUG DELIVERY SYSTEM BY HEMANTH

hi harsh thank you for the valuable comment. Pyrexia is different from hyperthermia. Pyrexia is rise in body temperature due to metabolites released by invading organism. This is under control of hypothalamus. Whereas hyperthermia is manual rise in temperature above the physiological range almost to 108o-114oF. Here temperature is raised to allow the release of liposomes. Complete release at a particular cell in one shot is not advisable. This has serious side effects of the drug itself. So the formulation is designed in such a way that it releases the drug at controlled rates. Since my topic is related to cancer therapy, i am giving you general answer with respect to this. We know the major side effect in using antineoplastics is they cause gastro intestinal disturbances due to eruption of GI lining. So before treatment if the patient is suffering from gastric problem, this must be treated first. For Cancers of stomach and other parts like peritoneum, Continuous Hyperthermic Peritoneal perfusion CHPP is applied. Ref.: Source: http://www.cancer.gov/cancertopics/factsheet/Therapy/hyperthermia

thank you..wish you good luck!!

hi anil thank you for the valuable comment Liposomes are mainly used as anticancer agents In heavy metal poisoning in cosmetics. In heavy metal poisoning, the charged chelating agent is entrapped within the liposome. These liposomes were taken up by the cells releasing the encapsulated agent-->Complexation process-->More soluble complex-->draining from the body. In cosmetics, the liposomes are used to retain the preparation to the outer layers of skin. Lets talk about the advantages first. Using thermosensitive liposomes the major positive thing is they cause minimal damage to non cancerous cells unlike the common chemotherapy and radiation methods. Hurdle in the present system of cancer therapy is myelosuppression, Hair loss, Emesis and so many. Major side effects can be reduced if the targeting is done to cancerous cells alone.

hello arun kumar thank you for the valuable comment. Therapeutic ratio is the ratio of amount of drug that produces therapeutic effect to the amount that produces toxic effect. Higher therapeutic index is always preferred. Improved metabolism to convert complex molecules into simpler ones. Improved therapeutic index to achieve better therapeutic effect of the drug. Both are in different scenarios. quaternary amine salt such as behentrimonium methosulfate used at a level of from 0.1% by weight when used as an emulsifier can produce MVS

hi arun kumar Liposomes are used in poisoning. In this case, the charged chelating agent is encapsulated in the liposomes --> complexation process--> producing more soluble compound--> elimination from the body. Coming to cosmetics keep aside the retention time. The main application of liposomes in cosmetics is AGEING. I hope you ve watched the new PONDS AND OLAY advertisements. Liposomes are used because the lipids get hydrated --> reduce drying of skin which is an early sign of ageing. Also liposomes are source to replenish lipids eg linoleic acid. Furthur information can be dealt in following link: http://www.dr-baumann-international.co.uk/science/Applications%20of%20Li... Retention times are measured using HPLC.

hi arun kumar thank you for the valuable comment Yes the technique is practiced all over the world. Infact, few people buy the ultrasound hyperthermia machine equipment. Good example is the following link where the man himself narrates his own story. nickshealth.blogspot.com/ Well, there is a time limit because excess vibrations may cause boils, blisters etc. However the time is selected based on stage of the cancer.

hello arun kumar thank you for the valuable comment Irritation here is the GI irritation which is a common side effect in chemotherapy. Whenever you raise the temperature definitely sweat is produced. This is the same thing in hyperthermia too.

hi arun kumar thank you for the valuable comment When the temperature is raised, the enzymatic activity is increased as we know. THis rise is continued upto threshold level. Local hyperthermia has a minimal action whereas systemic hyperthermia (Whole body hyperthermia) has vascular and cardiac side effects. So generally it is not practiced. As i said earlier, pH is determined whenever temperature is noted and it is designated as eg. pH 2.5 at 22oC So the patients with gastric acidity should be constantly monitored to combat the serious consequences.