Designing chemokineloaded temperaturesensitive liposomes. Liposomal delivery as a mechanism to enhance synergism. It has been known for several decades that the addition of cholesterol to a fluid phase bilayer mainly unsaturated lipids decrease. Method of removing the polymer that sterically stabilizes the liposomes against cell adhesion stealthing is controlled by temperature only. Tumorpenetrating peptideintegrated thermally sensitive. However, no significant change in calcein release profile was observed after replacement of a minor fraction of dspepeg with 0.
Temperature sensitive liposomes, triggered release, doxorubicin, protein, hyperthermia. When associated with liposomes, the peo moiety of the block copolymer is expected to inhibit liposomecell adhesion. Hence ph sensitive liposomes are prepared for different usage in drug delivery. Rapid release from lysolipid temperature sensitive liposomes j. To our knowledge, we first evaluated the role of double target heat release and. The temperature dependent effect can be strongly increased by the use of temperature sensitive liposomes in combination with regional hyperthermia, which specifically releases the entrapped drug in the heated. Temperature sensitive liposomes tsl were prepared via the wellknown lipid film hydration method as described. Developing temperature sensitive liposomes for targeted anticancer drug delivery is difficult to realize. Schematic representation of different thermosensitive liposome tsl systems. Formation of protein corona in vivo affects drug release. Pdf targeted temperature sensitive magnetic liposomes.
Us20070264322a1 method for making liposomes conjugated. Modeling of anticancer drug delivery by temperature. In contrast to the former thermosensitive formulations, ltsl release 100% of their contents within 20 seconds at the transition temperature. Temperature triggered nanotechnology for chemotherapy. Pulsedhigh intensity focused ultrasound and low temperature sensitive liposomes for enhanced targeted drug delivery and antitumor effect. Temperature sensitive liposomes tsl containing adriamycin adm and cytarabine arac were prepared. Thermosensitive liposomes tsls are a drug delivery system for targeted delivery that release the encapsulated drug when heated to fever temperatures. The temperature sensitive properties of pluronic f127 mw v12600, peo98ppo67peo98, a block copolymer or poloxamer, was used to control liposomecell adhesion. Eichhorn,3,5 hansjoerg eibl,6 nicole teichert,1 marcus schmittsody,5 rolf d. Liposomes have a characteristic t c transition temperature, at which they transit from gel phase to liquid crystalline phase.
Egg yolk phosphatidylcholine liposomes having these copolymers were prepared and their temperature sensitive contents release and association properties were investigated. Ltsls that are sensitive to mild, nondestructive temperature elevations above normal body temperature 4042 c has been investigated 14. The presented protocol describes the preparation of low temperature sensitive liposomes ltsls using a staggered herringbone micromixer shm. The temperature sensitive liposomes with or without luciferin did not show any membrane toxicity figure 2, or cause red blood cell aggregation at the concentrations tested from zero to 1mgml of lipids andor 5. Temperature sensitive liposomes tsl are liposomal drug carriers which release the contained drug in response to temperatures above 40c. Encapsulation efficiency of adm entrapped into tsl was about twice greater than that of arac. Development of temperature sensitive liposomes for. Thus, tsl facilitate targeted drug delivery when combined with localized hyperthermia, which can be mediated for example by focused ultrasound or radiofrequency rf ablation mediated heating 1, 2. Temperaturesensitive releases from liposomes containing. Congress onanother advantage of cationic liposomes is targeting of the liposomes to specific cells by conjugating the iiposomes with.
Current developments in drug delivery with thermosensitive liposomes. The basic idea was to administer this liposomal drug systemically, and then expose only. In order to develop a novel temperaturesensitive liposome, liposomes bearing poly nisopropylacrylamide, which shows a lower critical solution temperature. Targeted liposomes passive targeting conventional liposomes active targeting ligand strategies.
The permeability of the membrane increases significantly to promote the release of the encapsulated drugs from liposomes. Phase i trial of doxorubicincontaining low temperature. Therefore, the goal of this thesis was to develop a technology that was capable of directing immune cell migration in an effort to promote antitumor immunity and combat cancer growth. Temperature sensitive control of liposomecell adhesion. Temperaturetriggered nanotechnology for chemotherapy. At 34 degrees c, injecting free doxorubicin, a potent and clinically used chemotherapy drug, did not significantly slow tumor growth in mice compared to controls, the. Thermosensitive liposomes tsls have been an important research area in the field of tumor targeted. If you continue browsing the site, you agree to the use of cookies on this website. Preclinical evaluation of paramagnetic temperature sensitive. Liposomes as drug delivery system literature covering the components, classification, as well as the. Pdf thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or.
Liposomes for drug delivery durgavati yadav 1, kumar sandeep 2. The three liposomes were a standard nonthermosensitive liposome, a traditional temperature sensitive liposome triggered at 42 to 45 degrees c and dukes lowheat liposome. Above the lower critical solution temperature lcst of the polymer e. When exposed to temperatures at or above the lipid solidtoliquid phase transition temperature typically above 40. Motion compensated ultrasound imaging allows thermometry. Pdf novel temperaturesensitive liposomes with prolonged. Molecular targets and cancer therapeutics oct 2226, 2007. Heatsensitive liposome aids chemotherapy delivery to. Synthesis and characterisation of ultrasound imageable heatsensitive liposomes for hifu therapy. This ltsl was designed to release drug rapidly upon a temperature trigger using mild hyperthermia at 4142oc. As a model drug, dox was used as the chemotherapeutic agents, and the doxloaded irgdtargeted temperature sensitive liposomes were obtained.
Utilizing temperaturesensitive association of pluronic f. The temperature dependent effect can be strongly increased by the use of temperature sensitive liposomes in combination with regional hyperthermia, which specifically releases the entrapped drug in the heated tumor tissue. The temperaturedependent effect can be strongly increased by the use of temperaturesensitive liposomes in combination with regional hyperthermia, which specifically releases the entrapped drug in the heated tumor tissue. Alginate microspheres have been used for arterial embolization 30,31 and showed to be excellent embolization agents in the short term as well as the long term 28,31,32. Alginate microspheres containing temperature sensitive. In one embodiment, the process involves the incorporation of lipidlinkers to the surface of preformed liposomes, preferably at a higher temperature, followed. Calcium chloride loaded liposomes were prepared using the lipid film rehydration method.
Pdf synthesis and characterisation of ultrasound imageable heat. Targeted temperature sensitive magnetic liposomes for thermochemotherapy. Preparation and evaluation of temperature sensitive. The result indicates that dox molecules were retained tightly inside the liposomes and were effectively isolated from the body as long as the mild heating was not applied. Considering that the temperaturesensitive liposomes released encapsulated dox almost completely within 1 min at 45 c fig. Novel temperature sensitive liposomes containing hydrophobically modified polyn isopropylacrylamide hpnipam and their release behaviors were investigated using calcein as a fluorescence probe. It might be due to different polarity of the drugs. Targeted temperature sensitive magnetic liposomes for. In 1978, yatvin et al described the first temperaturesensitive formulation thermosensitive liposome, tsl that was able to release a hydrophilic drug when the temperature was increased a few degrees above physiological temperature. Liposomes a novel drug delivery system slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. Novel temperaturesensitive liposomes with prolonged circulation time lars h.
Targeted antibiotic delivery using low temperature. This can be achieved in vivo by local temperature control. Liposomes containing the ph sensitive lipid palmitoyl homocysteine phc were constructed so that the greatest ph differential 6. San francisco, ca c108 local delivery of therapeutic drugs will increase drug concentration at the site of treatment for maximum efficacy, and reduce systemic drug exposure. The encouraging results obtain in first phase of the clinical study of doxorubicin temperature sensitive liposomes. Specifically, we have packaged chemokines, signaling proteins that promote immune cell migration, inside temperature sensitive liposomes tsls. Its basic design to load and retain drug while evad. Such liposomes could be useful clinically if they enable drugs to be targeted to areas of the body in which ph is less than physiological, such.
These include the development of remote drug loading methodologies based on ph or ionic gradient, polyethylene glycolcoated long circulating liposomes, cationic liposomes for nucleic acid delivery, ph sensitive liposomes for cytosolic drug delivery, temperature sensitive liposomes for burst release in response to hyperthermia, and. Liposomes were made using egg phosphatidylcholine and different. Adm and arac were selected as model compounds of amphiphilic and hydrophilic drug, respectively. Pdf liposomes, sphereshaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid60s. Thermosensitive vesicles in controlled drug delivery for.
Open access nanoscale drug delivery and hyperthermia. Drug release kinetics of temperature sensitive liposomes. Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local. Temperature sensitive liposomes tsl are a promising drug delivery system for enhancing delivery of chemotherapy to solid tumors. Ltsls can achieve significantly improved drug accumulation and distribution in tumors compared to conventional treatment 85. C, pores are thought to form in the lipid membrane triggering release of the encapsulated drug 1 5. Temperature sensitization of liposomes by use of n. The complex interplay between heatbased cancer treatments such as thermal ablation and chemotherapy may require computational models to identify the relationship. Materials characterization of temperature sensitive liposomes. The present invention relates to a method of making a liposome composition. Targeted antibiotic delivery using low temperature sensitive liposomes and magnetic resonanceguided highintensity focused ultrasound hyperthermia rachel wardlow1, chenchen bing2, joshua vanosdol1, danny maples1, michelle ladouceurwodzak2, michele. Novel temperaturesensitive liposomes with prolonged. Pdf pulsedhigh intensity focused ultrasound and low. Hyperthermia increases the efficiency of various chemotherapeutic drugs and is administered as an adjunct to chemotherapy for the treatment of cancer patients.
Hyperthermia for the treatment of hepatic tumors in this study the effect of temperature sensitive liposomes was compared with. Chemoimmunotherapy of colon cancer with focused ultrasound and salmonella laden temperature sensitive liposomes thermobots skip to. Mathematical spatiotemporal model of drug delivery from. In particular, the invention relates to a method of making liposomes targeted to a specific cell receptor for delivery of a liposomeentrapped drug to the cell. Novel temperaturesensitive liposomes with prolonged circulation. In this thesis, we will investigate those liposomes that are activated upon entering regions of increased tissue temperature. Issels,1,2 and marc dellian4,5 1department of internal medicine iii, klinikum grosshadern medical center kgmc, ludwigmaximiliansuniversity, munich, germany. Lipids all have a temperature at which their fluidity changes. The presence of cholesterol exerts a profound influence on the properties of the lipid bilayers of the liposomes. Dualstimuli responsive liposomes using ph and temperaturesensitive polymers for controlled.
The discovery of phospholipids spontaneously forming spherical, selfclosed bubbles known as liposomes, upon dispersion in water, ushered a new era in drug delivery technology. A disposable microfluidic device for controlled drug. Temperature sensitive range of this method is not governed by the phase transition temperatures of lipid components. Dualstimuli responsive liposomes using ph and temperaturesensitive polymers for controlled transdermal delivery.
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