The use of petsliposomes significantly increased in vitro drug release versus pegfixed or pnipamaammodified liposomes. Smart thermosensitive liposomes stsls represent an interesting tool that can significantly improve the efficiency and accuracy of treating a broad category of diseases. Thermosensitive nanocarriers with long circulation properties can accumulate in the pathological sites by enhanced permeability and retention epr effect or attach targeting ligands to the surface of. On the other hand, our thermo sensitive polymermodified liposomes tpl can provide precise drug release using hydrophobicity change.
A new mechanism of thermal sensitivity for rapid drug release. A novel polymer modified thermosensitive liposome ptsl was developed for the delivery of doxorubicin dox for cancer therapy. Key targeting approaches for pharmaceutical drug delivery. Liposomes modified with temperatureresponsive polymers are tuned for cellular uptake. Pdf stimulusresponsive liposomes as smart nanoplatforms for. Thermosensitive polymermodified liposome as a multimodal and. The past decade has witnessed a massive surge of research interest in liposomes for delivery of therapeutic substances in animals. The application of thermosensitive nanocarriers in controlled. Here, we showed that the tunable surface properties of the temperatureresponsive polymer modified liposomes possibly enabled their dehydration by heating, which likely induced a faster cellular uptake and release. Localized delivery of doxorubicin in vivo from polymer modified thermosensitive liposomes with mrguided focused ultrasoundmediated heating t ta, e bartolaksuki, ej park, k karrobi, nj mcdannold, tm porter.
Preparation of temperaturesensitive liposomes for delivery of anticancer drugs by use of thermosensitive amphiphilic block copolymer kenji kono1, toshiaki ozawa1, chie kojima1, atsushi harada1, shokyoku kanaoka2, sadahito aoshima2. Paramagnetic thermosensitive liposomes have already been successfully studied in animal models and have demonstrated a clear correlation between tissue temperature changes and signal intensity changes in mri. Hyperthermiainduced antitumor activity of thermosensitive polymer modified temperaturesensitive liposomes. The polymermodified cationic liposomes revealed much lower zeta potential values below the lcst of the polymer than the unmodified cationic liposomes. Multifunctional theranostic nanoplatforms nps in response to environment stimulations for ondemand drug release are highly desirable. Quickresponsive polymerbased thermosensitive liposomes for.
Pdf optimum formulation of thermosensitive liposome for. Multifunctional thermosensitive liposomes based on natural. Temperatureresponsive polymermodified liposomes activated by heating are. Liposomes for drug delivery durgavati yadav 1, kumar sandeep 2, deepak pandey 3 and ranu kumari dutta 4 1 department of medicinal chemistry, ims, bhu, varanasi, india 2 department of preventive oncology, brairch, aiims, new delhi, india 3 department of reproductive biology, aiims, new delhi, india. Also, their behavior in the body and their toxicity have to be clarified. To obtain the polymer with anchoring groups to the liposome, a copolymer of nisopropylacrylamide and octadecyl acrylate 99. Evaluation of thermotriggered drug release in intramuscular.
Herein, the nearinfrared nirabsorbing dye, indocyanine green icg, and the antitumor drug, doxorubicin dox, were efficiently coencapsulated into the thermosensitive liposomes based on natural phasechange material. Stimulusresponsive nanopreparations for tumor targeting. Thermosensitive nanocarriers as the smart drug delivery systems have shown tremendous promise in the field of controlled drug delivery due to their special property. Focused ultrasoundmediated hyperthermia has long been studied as a noninvasive method of clinical targeted therapy, particularly for ablative applications. Thermosensitive hydrogel system with paclitaxel liposomes used in localized drug delivery system for in. Pdf localized delivery of doxorubicin in vivo from polymer.
Recently, we reported that 1,2dipalmitoylsnglycero3phosphoglyceroglycerol dppgog prolongs the circulation time of thermosensitive liposomes tsl. Liposomes are nanosized phospholipid vesicles that can serve as delivery platforms for a wide range of substances. The present study demonstrated that interactions of the thermosensitive polymer modified liposomes with model membranes and cells were suppressed by the hydrated polymer chains attached to the liposome surface below the lcst. So far, functional liposomes whose contents release behavior, surface properties, and affinity to cell surface can be controlled in a temperaturedependent manner, have been developed according to this strategy. Localized delivery of doxorubicin in vivo from polymermodified thermosensitive liposomes with mrguided focused ultrasoundmediated heating terence ta, a, 1 elizabeth bartolaksuki, b eunjoo park, c, 2 kavon m. Therefore, the biodistribution of the liposomes may be controlled by temperature. Copolymers containing temperatureresponsive nisopropylacrylamide nipaam and phresponsive propylacrylic acid paa were synthesized via reversible addition fragmentation chain transfer raft polymerization, yielding copolymers with dual phtemperature dependent.
Thermosensitive liposomes modified with poly nisopropylacrylamidecopropylacrylic acid copolymers for triggered release of doxorubicin. Thermosensitive nanocarriers with long circulation properties can accumulate in the pathological sites by enhanced permeability and retention epr effect or attach targeting ligands to the surface of the. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. To obtain temperaturesensitive liposomes which release their contents around the physiological temperature, we designed dioleoylphosphatidylethanolamine. These dppc liposomes become leaky to small water soluble molecules at a gelto liquid crystalline phase transition at the clinically achievable temperature of 41c 8. Temperaturecontrolled interaction of thermosensitive.
The reason that two lipids were used is because tsls were too leaky when only a. Ijms free fulltext effect of polymer phase transition. To mimic this strategy, nanopreparations designed to respond to particular stimuli such as acidity, redox potential, enzymes, hyperthermia, magnetic field, light, and ultrasound indicate the smartness in their antitumor applications. This cited by count includes citations to the following articles in scholar.
Stimulusresponsiveness is a natural characteristic of living organisms used to avoid damage from the environment. Copolymers containing temperatureresponsive nisopropylacrylamide nipaam and phresponsive propylacrylic acid paa were synthesized via reversible addition. A novel drug delivery system, enabling an in situ, thermally triggered drug release is described, consisting of an injectable thermoresponsive chitosan hydrogel containing doxorubicin. Thermosensitive liposomes in cancer therapy bentham science. Recent advances in nanomedicine have been studied in the veterinary field and have found a wide variety of applications. Temperaturecontrolled interaction of thermosensitive polymer. Thermosensitive polymermodified liposomes that release contents around physiological temperature.
Dehydrated copolymer chains strongly destabilize the liposomal membrane within a limited temperature range 4042. Porter, localized delivery of doxorubicin in vivo from polymermodified thermosensitive liposomes with mrguided focused ultrasoundmediated heating. Thermosensitive liposomes for mriguided drug delivery. K kono department of applied materials science, college of engineering, research institute for advanced science and technology, osaka, japan. A novel polymermodified thermosensitive liposome ptsl was developed for the delivery of doxorubicin dox for cancer therapy. Polymermodified and peptidesmodified thermosensitive liposomes. However, their zeta potential increased significantly above this temperature. Thermosensitive liposomes tsls are a drug delivery system for targeted delivery that release the encapsulated drug when heated to fever temperatures. Carbon nanotubeliposome supramolecular nanotrains for. Fractional laserassisted percutaneous drug delivery via. Mitochondriatargeting nearinfrared lighttriggered thermosensitive liposomes for localized photothermal and. Liposomes modified with temperatureresponsive polymers are.
The design, fabrication, characterization, and an assessment of in vitro bioactivity of this formulation is detailed. The thermosensitive hydrogel we prepared had an appropriate sol. These polymermodified thermosensitive liposomes ptsl demonstrated sensitivity to focused ultrasound, and required lower thermal doses and were more cytotoxic than traditional formulations in vitro. The examples of the polymer were disclosed in thermosensitive polymermodified liposome kono, k. Thermosensitive polymermodified liposomes polypeptide improving the efficiency of drug delivery requires the specific drug delivery at the target site. In vitro stability and content release properties of. Read thermosensitive polymer modified liposomes that release contents around physiological temperature, biochimica et biophysica acta biomembranes or bba biomembranes on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Current developments in drug delivery with thermosensitive. The thermoresponsive polymermodified liposomes exhibited high stability in serum solution at 37 c, as did peg modified liposomes, while the nonmodified liposomes aggregated rapidly. Novel temperaturesensitive liposomes having surface properties that can be controlled by temperature were designed as liposomes coated with polynisopropylacrylamide, which exhibits a hydrated coil to dehydrated globule transition at ca. Folate and conjugated gadolinium gd chelatemodified liposome shells enhance active targeting. Liposomes, sphereshaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid60s. Thermosensitive liposomes have been a popular area of investigation for several years leading to a plentitude of scientific literature and several patents.
Preparation of temperaturesensitive liposomes for delivery. Furthermore, petsliposomes also enhanced liposome stability in serum by inhibiting protein adsorption. Hyperthermiainduced antitumor activity of thermosensitive. Paramagnetic iron oxide nanoparticles are used to generate heat by applying alternative magnetic field to cause leakage of drugs in the liposomes. These polymer modified thermosensitive liposomes ptsl demonstrated sensitivity to focused ultrasound, and required lower thermal doses and were more cytotoxic than traditional formulations in vitro. Thermosensitive polymermodified liposomes, advanced drug. The discovery of phospholipids spontaneously forming spherical, selfclosed bubbles known as liposomes, upon dispersion in water, ushered a new era in drug delivery technology. Paramagnetic thermosensitive liposomes for mrthermometry. In summary, thermosensitive polymermodified petsliposomes plus external hyperthermia were found to be highly effective at enhancing the antitumor activity of dox. Thermosensitive polymermodified liposomes that release. Localized delivery of doxorubicin in vivo from polymermodified thermosensitive liposomes with mrguided focused ultrasoundmediated heating. Indeed, their performance has still to be improved. The present study demonstrated that interactions of the thermosensitive polymermodified liposomes with model membranes and cells were suppressed by the hydrated polymer chains attached to the liposome surface below the lcst. Abstractliposomes are used for transdermal delivery of drugs and vaccines.
Drug release from thermosensitive liposomes by applying an. Thermosensitive polymermodified liposomes that release contents. The application of thermosensitive nanocarriers in. Dual controlled delivery of gemcitabine and cisplatin. As a service to our customers we are providing this early version of the manuscript. In addition, thermosensitive polymermodified liposomes offer a new attractive strategy for drug targeting.
Another polymer used for the polymermodified tsl preparation has been poly22ethoxy ethoxyethyl vinyl ether peoeove. Therefore, the liposomes could be highly applicable for improving intracellular drugdelivery carriers. The effect of polymer backbone chemistry on the induction of. Pdf chemical components for the design of temperature. Thermosensitive polymers present a low critical solution temperature. Localized delivery of doxorubicin in vivo from polymer modified thermosensitive liposomes with mrguided focused ultrasoundmediated heating.
The temperatureresponsive liposomes exhibited cellular uptake at 42 c, but were not taken up into cells at 37 c. These liposomes have been prepared using lipids whose membranes undergo a geltoliquid crystalline phase transition a few degrees above. Conventional thermosensitive liposomes, such as a geltoliquidcrystalline transitionbased material, have the potential shortcoming that drug molecules may leak through the incomplete membrane of the liposome. Temperaturecontrol of interactions of thermosensitive. Thermo sensitive polymers present a low critical solution temperature. Polymermodified thermosensitive liposomes one of the most effective methods for heat sensitizing of the liposome is to incorporate synthetic and naturally occurring polymers in lipid composition, in which the liposome membrane undergo a temperaturedisruptive effect because of conformational changes in response to temperature change. These features of the thermosensitive polymer modified liposomes may allow their use as a new drug delivery system with temperaturecontrolled functionalities which the conventional temperaturesensitive liposomes do not possess. Thermosensitive liposomes for localized delivery and triggered. Tunable surface properties of temperatureresponsive polymer. Thermosensitive liposomes encapsulating paramagnetic iron oxide nanoparticles are used as a drug controlled release system.
The copolymer displayed a thermosensitive transition at a lower critical. Nov 28, 2014 these polymer modified thermosensitive liposomes ptsl demonstrated sensitivity to focused ultrasound, and required lower thermal doses and were more cytotoxic than traditional formulations in vitro. The unmodified cationic liposomes did not change its zeta potential between 2060c. Multimodal targeted high relaxivity thermosensitive. Since the only tsl formulation in clinical trials applies dspepeg2000 and lysophosphatidylcholine plysopc, the objective of this study was to compare the influence of these lipids with dppgog on in vitro stability and.
Oct 25, 20 for thermosensitive liposomal preparations, dipalmitoylphosphatidylcholine dppc can be used as a primary lipid. These features of the thermosensitive polymermodified liposomes may allow their use as a new drug delivery system with temperaturecontrolled functionalities which the conventional temperaturesensitive liposomes do not possess. Temperaturecontrolled interaction of thermosensitive polymer modified cationic liposomes with negatively charged phospholipid membranes. Read temperaturecontrolled interaction of thermosensitive polymermodified cationic liposomes with negatively charged phospholipid membranes, biochimica et biophysica acta biomembranes or bba biomembranes on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Its abilities with regard to morphological and functional tumor characterization without exposure to ionizing radiation are well known, and it is a standard method in clinical use. Two approaches for overcoming the factors related to the. Targeted bioavailability of drugs by triggered release from liposomes. Jan 01, 2009 the surface of the thermosensitive liposomes can be modified by some polymer to further tune the thermosensitive temperature of the thermosensitive liposomes. Mri is the method of choice for imageguided drug delivery with tsl.
Nevertheless, before entering clinical trials they have to be studied in more detail with regard to dose, pharmacokinetics and toxicity. Pdf liposomes are known to be promising nanoparticles nps for drug delivery. Thermosensitive vesicles in controlled drug delivery for. Materials and methods animals and treatment groups study design rabbits bearing a vx2 tumour in one thigh were administered tld either with or without 20min of mild hyperthermia to a. Another approach for sensitizing liposomes to temperature is to incorporate synthetic polymers that. These liposomes are now often termed as traditional thermosensitive liposomes ttsls 6. While mostly investigated as cancer therapy, other applications including treatment of local infections and wound healing. Focused ultrasound hyperthermia for targeted drug release. Recent developments in liposomebased veterinary therapeutics. T1 hyperthermiainduced antitumor activity of thermosensitive polymer modified temperaturesensitive liposomes. Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. The temperaturesensitive liposome is now in phase i human clinical trials. Evaluation of thermotriggered drug release in intramusculartransplanted tumors using thermosensitive polymer modified liposomes and mri.
Thermosensitive polymermodified liposomes sciencedirect. Dec 31, 2001 so far, functional liposomes whose contents release behavior, surface properties, and affinity to cell surface can be controlled in a temperaturedependent manner, have been developed according to this strategy. Thermosensitive hydrogel system with paclitaxel liposomes. Us20090004258a1 drug release from thermosensitive liposomes. The reason that two lipids were used is because tsls were too leaky when only a single lipid was used. Since pure dppc liposomes inevitably lead to incomplete drug release, other phospholipids. In this regard, various types of stimulisensitive materials have been designed, such as ph, light and temperaturesensitive polymers. Temperaturecontrolled interaction of thermosensitive polymermodified.
Liposomes resemble cell membranes in their structure and composition. However, recently, temperaturesensitization of liposomes has been attempted using thermosensitive polymers. Nov 27, 2012 there is growing interest in the development of artificial moleculartransport systems. Localized delivery of doxorubicin in vivo from polymermodified thermosensitive liposomes with mrguided.
Novel approaches to treatment of hepatocellular carcinoma and. More recently, the use of ultrasound to induce mild hyperthermia temperature elevations. The in vivo efficacy of thermosensitive liposome encapsulated taxol was determined in b16f10 murine melanoma transplanted into c57bi6 mice in combination with local hyperthermia. For instance, drug release from lysolipidcontaining thermosensitive liposomes ltsls occurs by generation of stabilised defects in. Recent advances on thermosensitive and phsensitive. Temperaturedependent associating property of liposomes. Pdf localized delivery of doxorubicin in vivo from. Combined with localized hyperthermia, tsls allow precise drug delivery to a targeted region.
Our objective was to develop temperatureresponsive tr liposomes to achieve temperaturedependent, controlled release of an encapsulated drug, and use fractional laser irradiation to enhance transdermal permeability of these liposomes. The ones marked may be different from the article in the profile. 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. The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. The polymer modified liposomes pmtl could cocarry and release gemcitabine gem and cisplatin cis in a thermally controlled rate and were also found to exhibit specific hydrophobic interactions with the cell membranes above the temperature transition of the formulations.
Department of biomedical engineering, boston university, boston, ma 02215, department of bioengineering, university of washington, seattle, wa 98195. Hyperthermiainduced antitumor activity of thermosensitive polymer modified temperaturesensitive liposomes hee dong han, min soo choi, taewon hwang, chung kil song, hasoo seong, tae woo kim, ho suk choi, byung cheol shin. Optimum formulation of thermosensitive liposome for targeted tumor drug delivery article pdf available in journal of takeda research laboratories 51. The copolymer displayed a thermosensitive transition at a lower critical solution.