Radiation sensitive liposomes pdf

Magnetic resonance imaging of temperaturesensitive liposome. Heatresponsive drug delivery, which takes advantage of lowmelting point of membrane lipids, has attracted increasing attention because of its lowtoxicity 9, 10. Detection of sunlight exposure with solarsensitive liposomes. Efficacy of liposomes and hyperthermia in a human tumor xenograft model. Thermodoxa temperature sensitive liposomes at phase iii is a cholesterol free liposome.

A disposable microfluidic device for controlled drug release from thermal sensitive liposomes by high intensity focused ultrasound. We previously reported sapsplipo, tumor microenvironmentsensitive liposomes, are effectively delivered to tumor tissue hama et al. Radiation sensitive liposomes possess the ability to localize at tumor sites due to increased permeability of the vasculature near tumor associated areas. Keywords singlewalled carbon nanotubes, thermo sensitive liposomes, doxorubicin, tumortargeting, nearinfrared radiation introduction. Liposomal drug delivery systems and anticancer drugs. Drugencapsulating egf sensitive liposomes for egfoverexpressing cancer therapies by albert wong honors b. Current drugs are effective once they reach the diseased area but need assistance in their delivery. Schematic representation of different thermosensitive liposome tsl systems. In particular, the invention encompasses a liposomal delivery system, comprising a stable liposomeforming lipid and a polymerizable colipid, a fraction of which polymerizable colipid polymerizes upon exposure to ionizing, radiation, thereby destabilizing the liposomal membrane. Heat sensitive liposomes melt to varying degrees when heated, allowing the drug inside to escape. Long meng 1, zhiting deng 1, lili niu 1, fei li 1, fei yan 1, junru wu 2, feiyan cai 1, hairong zheng 1. Light sensitive liposomes explored since early 1980s have lately regained attention.

Since then, liposomes have made their way to the market. Thermosensitive vesicles in controlled drug delivery for. Us10220000b2 methods and compositions for xray induced. Research focused on the clinical and therapeutic side of ph. Liposomes are a novel drug delivery system ndds, they are vesicular structures consisting of bilalyers which form spontaneously when phospholipids are dispersed in water. Preliminary studies on xraysensitive liposome request pdf. These conditions are suitable for the destabilization of radiation sensitive liposomes that are sterically stabilized. A new temperaturesensitive liposome for use with mild. Radiation sensitive liposomes and temperature sensitive liposomes are formulated by using saturated lipids. Here, the authors design xray triggered druggeneloaded liposomes by embedding. Only tumor blood vessels have gaps in them that allow the passive leaking of liposomes, explained dewhirst, professor of radiation oncology. They are caused when repeated doses of radiation pass through the skin.

Compared with conventional liposomes, sapsplipo could be delivered to deeper regions within both spheroids and tumor tissues. Carriers drug delivery systems often rely on a carrier to achieve these goals. Heatsensitive liposome aids chemotherapy delivery to. Tumor microenvironmentsensitive liposomes penetrate tumor. Muscle and nerve cells were re latively insensitive to radiation, and therefore, so are the muscles and the brain. Liposomes have been extensively used in the past decade as drug carriers. Liposomes containing the ph sensitive lipid palmitoyl homocysteine phc were constructed so that the greatest ph differential 6. For example, ionizing radiation can stimulate the release of liposomal contents. Controlled gene and drug release from a liposomal delivery platform.

The first step was optimizing a lipid composition for temperature sensitivity using a calcein release assay. This method employs mild conditions and is capable of efficient entrapment of a wide range of macromolecules, such as proteins. Each section explores the mechanisms of drug release that can be achieved using liposomes in conjunction with the external trigger. Destabilization of liposomes allows for leakage of liposomal contents. Magnetic resonance imaging of temperaturesensitive. Liposomes, sphereshaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid60s. Liposomes are versatile in that the entire membrane of the liposome can be composed of either. Electromagnetic radiationsensitive liposomes present a promising.

The development of imaging applications with radioactive liposomes is widely described 9, 10, but their advantages for carrying therapeutic radionuclides for cancer therapy could be further. Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. The development of targeted and triggerable delivery systems is of high relevance for anticancer therapies. It uses lyophilization and is scalable in both steps of. Targeted temperature sensitive magnetic liposomes for thermo. Combined external beam irradiation and external regional hyperthermia. We found that tsls improved the tumorspecific delivery of boronophenylalanine bpa and boronated 2nitroimidazole derivative b381 in d54 glioma cells. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Reductionsensitive liposomes from a multifunctional lipid. Methods and protocols, leading experts in the related fields explore cuttingedge experimental methods involving all aspects of lipids as essential components of the cell membrane. Here we report xraytriggerable liposomes incorporating gold nanoparticles and photosensitizer verteporfin. In parallel, the nonultrasound sensitive liposomal formulations nusl.

Treatment fields are the parts of the body that are treated with radiation. The single biggest challenge now facing drug delivery for liposomes and indeed other carriers is to initiate and produce release of the encapsulated drug only at the diseased site and at controllable rates. The release rate of doxorubicin from ph sensitive liposomes was faster at ph 4 than at ph 7. Journal of biomaterials applications thermosensitive. An in vitro assessment of liposomal topotecan simulating. Photoreactive lipid molecules provide an opportunity to generate stable nanodelivery vehicles for sustained release of drugs in circulation together with phototriggerable systems for localized drug delivery. Contents of these liposomes are most often destined for lysosomes new, 1990. In particular, the invention encompasses a liposome composition comprising a stable liposomeforming lipid and a polymerizable colipid, and a chain transfer agent. Report of the independent advisory group on nonionising radiation. Skin reactions from radiation treatments skin reactions are a common side effect of radiation treatments. For instance, coating peg onto liposomes is a helpful approach that can prevent liposome engulfment by the macrophages. Thermal sensitive liposomes improve delivery of boronated.

Id and roman lechowski department of small animal diseases with clinic, faculty of veterinary medicine, warsaw university of life sciences, nowoursynowska 159c, 02776 warsaw, poland. An in vitro assessment of liposomal topotecan simulating metronomic chemotherapy in combination with radiation in tumorendothelial spheroids skip to. Thus, it is not inconceivable that radiationsensitive liposomes could be incorporated into preexisting treatment plans for concurrent use with. These liposomes fuse with cells when the ph is low, thus. The presence of cholesterol exerts a profound influence on the properties of the lipid bilayers of the liposomes. The permeability of the membrane increases significantly to promote the release of the encapsulated drugs from liposomes. Doxorubicin is actively loaded and retained in temperaturesensitive liposomes by using a ph gradientdriven loading protocol that includes mnso 4.

Drug release will be triggered by hyperthermia upon local application of an ac magnetic field on the tumor tissue. State of the art article pdf available december 2012 with 25,180 reads how we measure reads. It has been known for several decades that the addition of cholesterol to a fluid phase bilayer mainly unsaturated lipids decrease. As a drug delivery system, these drugencapsulating liposomes. In vivo monitoring of tissue pharmacokinetics of liposome.

The temperaturesensitive liposome is now in phase i human clinical trials. A disposable microfluidic device for controlled drug release. They are microscopic vesicles in which an aqueous volume is entirely enclosed by a membrane composed of lipid bilayers. The use of liposomes and nanoparticles as drug delivery systems to improve cancer treatment in dogs and cats katarzyna zabielskakoczywas. When desert plants dehydrate from lack of water, this remarkable molecule takes the place of moisture. Open access nanoscale drug delivery and hyperthermia. Sterilizing with chemicals is not a viable option either, as it may affect the stability of the liposomes. This product profile is intended only for professional use and is not to be published to retail consumers 1800089 2454929 activating liposome complex with nayad continued paired with the silver ear mushroom is trehalose, an antioxidant found in desert resurrection plants. Desired properties of efficient carriers include the ability to evade the mononuclear phagocyte system mps to prolong the circulation halflife t12, and preferential release of the encapsulated drug at the targeted site. Optical spectroscopy was performed prior to therapy, immediately after treatment, and 6. Desired properties of efficient carriers include the ability to evade the mononuclear phagocyte system mps to prolong the circulation halflife t12, and preferential release of the encapsulated drug at the. A novel class of phototriggerable liposomes containing dppc.

Biology the university of texas at arlington, 2005 submitted to the harvardmit division of health sciences and technology in partial fulfillment of the requirements for the degree of master of health sciences and technology at the. We hypothesized that, due to the attachment of hauns, the liposomes can present the photothermal effect, and consequently a controlled release of the drug by a nir laser light irradiation as. Is it necessary to add cholesterol to a liposome formulation. The cellular uptake of liposomes is generally believed to be mediated by adsorption of liposomes onto the cell surface and subsequent endocytosis. Reactor concepts manual biological effects of radiation. In vivo monitoring of tissue pharmacokinetics of liposomedrug using mri. In this work, we describe the preparation and characterization of liposomes using the dehydrationrehydration process developed by gregoriadis and kirby 1984. We report here on reduction sensitive liposomes composed of a novel multifunctional lipidlike conjugate, containing a disulfide bond and a biotin moiety, and natural phospholipids. Pdf phsensitive liposomes for drug delivery in cancer treatment. Fda has previously approved stealth liposomes for the delivery of doxorubicin for the treatment of breast cancer and ovarian cancer 14. As a result, more tumor cells are killed by irradiation, while.

By using two temperature sensitive liposomes ttsls and ltsls that have different triggering temperature ranges and release rates, we were able to explore the role of httriggered liposomal drug release in drug. As a result, more tumor cells are killed by irradiation, while the toxicity for healthy cells remains unchanged. Lightsensitive lipidbased nanoparticles for drug delivery. Optical spectroscopy was performed prior to therapy, immediately after treatment, and 6, 12, and 24h post therapy. Preclinical and clinical testing of low temperature sensitive liposomes used in combination with mild hyperthermia in the treatment of local cancer chelsea d. These drugencapsulating liposomes remain inert until they are exposed to an abnormal concentration of egf. However, the external excitation with electromagnetic radiation re. A disposable microfluidic device for controlled drug. Normally, the bulk of liposomes together with their encapsulated material will enter the lysosomal pathway, where it will be exposed to a large panel of lytic. In terms of radiation sensitivity, the drug leak rate of the xraysensitive doxloaded liposome increased gradually and peaked at 65. The membranes of these liposomes are composed of either cholesterol hemisuccinate. Thermosensitive liposomes tsls are a drug delivery system for targeted delivery that release the encapsulated drug when heated to fever temperatures.

Publishers pdf, also known as version of record includes final page. For all sizes of liposomes, the relaxivity of the entrapped gddtpa was less than that of free gddtpa. Compositions including ph sensitive lipid vesicles comprised of a lipid layer, an agent, and an organic halogen such that the agent is released from the vesicles after exposure to ionizing radiation. Dewhirst1,4 the purpose of this study was to determine if mnso. The sterilization of liposomes is a complicated conundrum, as liposomes are sensitive to high temperatures and certain methods of radiation. Pdf liposomes, sphereshaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid60s. One tumour was selected for local hyperthermia and subsequent systemic treatment. Each section explores the mechanisms of drug release that can be achieved. Combined modality therapy based on hybrid gold nanostars coated with temperature sensitive liposomes to overcome paclitaxelresistance in hepatic carcinoma by hongyan zhu 1, weili han 1, ye gan 1, qiaofeng li 2,3, xiaolan li 2,4, lanlan shao 1, dan zhu 4, and hongwei guo 2,4. In this study, targeted temperature sensitive magnetic liposomes have been prepared and characterized for their intended use in thermochemotherapy of cancer. Tumor microenvironment sensitive liposomes penetrate tumor tissue via attenuated interaction of the extracellular matrix and tumor cells and accompanying actin depolymerization satoko suzuki, shoko itakura, ryo matsui, kayoko nakayama, takayuki nishi, akinori nishimoto, susumu hama, and kentaro kogure. Dec 10, 2009 therapeutic doses of ionizing radiation can substantially enhance the release of encapsulated water soluble or lipid associated molecules from radiation sensitive liposomes. In this paper, the preparation and in vitro characterization of combined targeting of temperature sensitive magnetic liposomes by folate receptor and magnetic field for thermochemotherapy of cancer are reported.

Preclinical evaluation of paramagnetic temperature sensitive. Preparation, characterization and applications of liposomes. This report examines the effect of liposome surface charge on liposomal binding and endocytosis in two different cell lines. Smart micronsize drugencapsulating epidermal growth factor egf sensitive liposomes for egfoverexpressing cancer therapies have been developed and studied. Detection of sunlight exposure with solarsensitive. Systemic antitumour effects of local thermally sensitive. Novel temperaturesensitive liposomes with prolonged circulation. The liposomes were designed based on a thermal sensitive liposome tsl formulation, and hauns were attached onto the membrane of the liposomes fig.

Small unilamellar liposomes were obtained with appropriate polydispersity and stability. Dewhirst,1,2,3 1department of pathology, 2department of radiation oncology, 3department of biomedical engineering, duke univer. With nearly one hundred years of intensive study, lipids have proven to be a vital and evermorepromising area of cell biological research. Therefore, the selection of the most appropriate lipids e. Spatially specific liposomal cancer therapy triggered by clinical. Methods of delivering the agent to a target in a subject using the compositions provided herein are also described. A variety of light sensitive nanoparticles and materials has been developed in recent years. Liposomes of 70400 nm diameter containing gddtpa were prepared by a freezethaw extrusion process. Before the liposomes can become useful carriers, they must.

Spatially specific liposomal cancer therapy triggered by. These exhibited high trapping efficiencies and excellent stability during storage. Such delivery implies for selective and effective localization of pharmacological active moiety at preidentified eg. The use of liposomes and nanoparticles as drug delivery. Yasumasa nishimura, koji ono, masahiro hiraoka, shinichirou masunaga, shiken jo, yuta shibamoto, keisuke sasai, mitsuyuki abe, katsumi iga, and yasuaki ogawa 1990 treatment of murine scc vii tumors with localized hyperthermia and temperature sensitive liposomes containing cisplatin. Wo2001039744a3 pctus2000032902 us0032902w wo09744a3 wo 2001039744 a3 wo2001039744 a3 wo 2001039744a3 us 0032902 w us0032902 w us 0032902w wo 09744 a3 wo09744 a3 wo 09744a3 authority wo wipo pct prior art keywords liposome liposomal radiation sensitive present invention sensitive liposomes prior art date 19991. A variety of lightsensitive nanoparticles and materials has been developed in recent years.

Furthermore, drugs entrapped in liposomes can be released in response to diverse stimuli such as variation in ph, electromagnetic radiation light excitation, local enzymes and heat enhancement 58. The ph sensitive liposomes killed 70% of the tumor cells but did not cause injury to the normal cells. The membranes of these liposomes are composed of either cholesterol hemisuccinate chems, phosphatidyl ethanolamine pe, oleic acid oa or dioleoylphosphatidyl ethanolamine dope. Targeted temperature sensitive magnetic liposomes for. Nearinfrared light sensitive liposomes for the enhanced. Controlled gene and drug release from a liposomal delivery. Temperature sensitive control of liposomecell adhesion.

Pdf in recent years, liposomes have been employed with growing success as pharmaceutical carriers for antineoplastic drugs. The present invention relates to a radiation sensitive liposome, and the use of this liposome as carrier for therapeutic and diagnostic agents. Targeted bioavailability of drugs by triggered release from liposomes. Bleomycinloaded phsensitive polymerlipidincorporated. When ph sensitive molecules are incorporated into liposomes, drugs can be specifically released from these vesicles by a change of ph in the ambient serum. Pharmaceutics free fulltext combined modality therapy. The release of encapsulated or associated agents from liposomes may occur passively or may be stimulated or induced. Schematic depiction of a temperaturesensitive liposome containing doxorubicin dox and contrast agent manganese sulfate, mnso 4.