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Thermosensitive liposomes

Joshua VanOsdol, Kalyani Ektate, Selvarani Ramasamy, Danny Maples, Willie Collins, Jerry Malayer, Ashish Ranjan
Mild hyperthermia generated using high intensity focused ultrasound (HIFU) and microbubbles (MBs) can improve tumor drug delivery from non-thermosensitive liposomes (NTSLs) and low temperature sensitive liposomes (LTSLs). However, MB and HIFU are limited by the half-life of the contrast agent and challenges in accurate control of large volume tumor hyperthermia for longer duration (>30min.). The objectives of this study were to: 1) synthesize and characterized long-circulating echogenic nanobubble encapsulated LTSLs (ELTSLs) and NTSLs (ENTSLs), 2) evaluate in vivo drug release following short duration (~20min each) HIFU treatments administered sequentially over an hour in a large volume of mouse xenograft colon tumor, and 3) determine the impact of the HIFU/nanobubble combination on intratumoral drug distribution...
December 30, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Tao Lu, Timo L M Ten Hagen
Thermosensitive liposomes (TSL) receive attention due to their rapid externally controlled drug release at transition temperature in combination with hyperthermia. This rapid release feature of TSL occurs when the liposome membrane is going through a phase change which results in numerous interfaces, at so-called crystal grain boundaries. Based on experience with TSLs, our group found that thermosensitive liposomes formulated by binary compositions of DPPC and DSPC at proper ratios are able to exhibit rapid release without incorporation of release-promoting components...
December 29, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Zahraa Al-Ahmady, Neus Lozano, Kuo-Ching Mei, Wafa' T Al-Jamal, Kostas Kostarelos
The engineering of responsive multifunctional delivery systems that combine therapeutic and diagnostic (theranostic) capabilities holds great promise and interest. We describe the design of thermosensitive liposome-nanoparticle (NP) hybrids that can modulate drug release in response to external heating stimulus. These hybrid systems were successfully engineered by the incorporation of gold, silver, and iron oxide NPs into the lipid bilayer of lysolipid-containing thermosensitive liposomes (LTSL). Structural characterization of LTSL-NP hybrids using cryo-EM and AFM revealed the incorporation of metallic NPs into the lipid membranes without compromising doxorubicin loading and retention capability...
November 30, 2016: International Journal of Pharmaceutics
Jonathan P May, Eno Hysi, Lauren A Wirtzfeld, Elijus Undzys, Shyh-Dar Li, Michael C Kolios
Imaging methods capable of indicating the potential for success of an individualized treatment course, during or immediately following the treatment, could improve therapeutic outcomes. Temperature Sensitive Liposomes (TSLs) provide an effective way to deliver chemotherapeutics to a localized tumoral area heated to mild-hyperthermia (HT). The high drug levels reached in the tumor vasculature lead to increased tumor regression via the cascade of events during and immediately following treatment. For a TSL carrying doxorubicin (DOX) these include the rapid and intense exposure of endothelial cells to high drug concentrations, hemorrhage, blood coagulation and vascular shutdown...
2016: PloS One
Hugh S O'Neill, Caroline C Herron, Conn L Hastings, Roel Deckers, Adolfo Lopez Noriega, Helena M Kelly, Wim E Hennink, Ciarán O McDonnell, Fergal J O'Brien, Eduardo Ruiz-Hernández, Garry P Duffy
: Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome retention, thus providing a prolonged release in target tissues. Moreover, release can be controlled through the use of a minimally invasive external hyperthermic stimulus. Temporal control of release is particularly important for complex multi-step physiological processes, such as angiogenesis, in which different signals are required at different times in order to produce a robust vasculature...
October 20, 2016: Acta Biomaterialia
Xiejun Xu, Xingqing Xiao, Shouhong Xu, Honglai Liu
Recent experiments in our lab (Phys. Chem. Chem. Phys., 2016, 18, 10129-10137) suggested using leucine zipper peptides to enhance the thermosensitivity of liposomes. To understand the mechanisms of temperature-responsive control by the leucine zipper peptide in liposomes, we firstly performed quantum mechanics calculations and implicit-solvent replica exchange molecular dynamics simulations to study the thermo-stability of two leucine zipper peptides, CH3(CH2)4-CO-[VAQLEVK-VAQLESK-VSKLESK-VSSLESK] (termed the capped peptide) and A-[VAQLEVK-VAQLESK-VSKLESK-VSSLESK] (termed the ALA peptide)...
September 14, 2016: Physical Chemistry Chemical Physics: PCCP
Tanguy Boissenot, Alexandre Bordat, Elias Fattal, Nicolas Tsapis
Ultrasound-triggered drug delivery is now becoming a mature technology with first patients enrolling in clinical trials. Having a clear overview of the field is complicated as it mixes ultrasound physics and biological effects, particle formulation, and pharmacokinetics and biodistribution. The scope of this review is to move from basics to the latest developments of combined techniques using ultrasound for triggering drug release. Generalities on ultrasound are first given to better understand the parameters on which the clinician can operate to modulate the amount of delivered energy...
November 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Simone Schuerle, Jaideep S Dudani, Michael G Christiansen, Polina Anikeeva, Sangeeta N Bhatia
Targeted cancer therapies require a precise determination of the underlying biological processes driving tumorigenesis within the complex tumor microenvironment. Therefore, new diagnostic tools that capture the molecular activity at the disease site in vivo are needed to better understand tumor behavior and ultimately maximize therapeutic responses. Matrix metalloproteinases (MMPs) drive multiple aspects of tumorigenesis, and their activity can be monitored using engineered peptide substrates as protease-specific probes...
October 12, 2016: Nano Letters
Katja Zimmermann, Martin Hossann, Johannes Hirschberger, Karin Troedson, Michael Peller, Moritz Schneider, Andreas Brühschwein, Andrea Meyer-Lindenberg, Gerhard Wess, Melanie Wergin, René Dörfelt, Thomas Knösel, Markus Schwaiger, Christine Baumgartner, Johanna Brandl, Sabine Schwamberger, Lars H Lindner
PURPOSE: Doxorubicin (DOX)-loaded phosphatidyldiglycerol-based thermosensitive liposomes (DPPG2-TSL-DOX) combined with local hyperthermia (HT) were evaluated in cats with locally advanced spontaneous fibrosarcomas (soft tissue sarcoma, STS). The study was designed to evaluate the safety and pharmacokinetic profile of the drug. Results from four dose-levels are reported. METHODS: Eleven client-owned cats with advanced STS were enrolled. Five cats received escalating doses of 0...
September 4, 2016: International Journal of Hyperthermia
Kalyani Ektate, Ankur Kapoor, Danny Maples, Ahmet Tuysuzoglu, Joshua VanOsdol, Selvarani Ramasami, Ashish Ranjan
Ultrasound imaging is widely used both for cancer diagnosis and to assess therapeutic success, but due to its weak tissue contrast and the short half-life of commercially available contrast agents, it is currently not practical for assessing motion compensated contrast-enhanced tumor imaging, or for determining time-resolved absolute tumor temperature while simultaneously reporting on drug delivery. The objectives of this study were to: 1) develop echogenic heat sensitive liposomes (E-LTSL) and non-thermosensitive liposomes (E-NTSL) to enhance half-life of contrast agents, and 2) measure motion compensated temperature induced state changes in acoustic impedance and Laplace pressure of liposomes to monitor temperature and doxorubicin (Dox) delivery to tumors...
2016: Theranostics
Wouter J M Lokerse, Michiel Bolkestein, Timo L M Ten Hagen, Marion de Jong, Alexander M M Eggermont, Holger Grüll, Gerben A Koning
Doxorubicin (Dox) loaded thermosensitive liposomes (TSLs) have shown promising results for hyperthermia-induced local drug delivery to solid tumors. Typically, the tumor is heated to hyperthermic temperatures (41-42 °C), which induced intravascular drug release from TSLs within the tumor tissue leading to high local drug concentrations (1-step delivery protocol). Next to providing a trigger for drug release, hyperthermia (HT) has been shown to be cytotoxic to tumor tissue, to enhance chemosensitivity and to increase particle extravasation from the vasculature into the tumor interstitial space...
2016: Theranostics
Azadeh Haeri, Sara Zalba, Timo L M Ten Hagen, Simin Dadashzadeh, Gerben A Koning
The epidermal growth factor receptor (EGFR) is a promising target for anti-cancer therapy. The aim of this study was to design thermosensitive liposomes (TSL), functionalized with anti-EGFR ligands for targeted delivery and localized triggered release of chemotherapy. For targeting, EGFR specific peptide (GE11) and Fab' fragments of cetuximab were used and the effect of ligand density on in vitro tumor targeting was investigated. Ligand conjugation did not significantly change the physicochemical characteristics of liposomes...
October 1, 2016: Colloids and Surfaces. B, Biointerfaces
Yanfang Yang, Xiangyang Xie, Xueqing Xu, Xuejun Xia, Hongliang Wang, Lin Li, Wujun Dong, Panpan Ma, Yang Yang, Yuling Liu, Xingguo Mei
Due to the absence of effective in vivo delivery systems, the employment of small interfering RNA (siRNA) in the clinic has been hindered. Here, we describe a novel siRNA targeting system that combines features of biological (cell-permeable peptides, CPPs) and physical (magnetic) siRNA targeting for use in magnetic hyperthermia-triggered release. A siRNA-CPPs conjugate (siRNA-CPPs) was loaded into thermal and magnetic dual-responsive liposomes (TML) (siRNA-CPPs/TML), and in vitro siRNA-CPPs thermosensitive release activity, targeted cellular uptake, gene silencing efficiency, in vivo targeted delivery and in vivo antitumor activity were determined...
October 1, 2016: Colloids and Surfaces. B, Biointerfaces
Chunying Zeng, Fanglin Yu, Yang Yang, Xiaohui Cheng, Yan Liu, Hui Zhang, Shiqing Zhao, Zhenbo Yang, Mingyuan Li, Zhiping Li, Xingguo Mei
Oxaliplatin (OXP) was reported to show low anti-tumor activity when used alone and to display side effects; this low activity was attributed to high partitioning to erythrocytes and low accumulation in tumors. Thermosensitive liposomes (TSL) were considered able to specifically deliver drugs to heated tumors and to resolve the OXP distribution problem. Regretfully, TSL encapsulating doxorubicin did not demonstrate significant improvement in progression-free survival. Drug release below 41°C and significant leakage were considered major reasons for the failure...
2016: PloS One
Shuangxia Ren, Yu Dai, Cuiyun Li, Zhixia Qiu, Xin Wang, Fengjie Tian, Sufeng Zhou, Qi Liu, Han Xing, Yang Lu, Xijing Chen, Ning Li
In situ gelling thermosensitive hydrogel formulation has been reported to effectively sustain the release of macromolecules for a long time. However, the low-molecular-weight hydrophilic drugs, such as doxorubicin (DOX), are not suitable for intratumoral injection because the release will complete within one day. In this study, liposomal doxorubicin (LipDOX) was added into the hydrogel to form a novel thermosensitive formulation which prolonged the sustained release of DOX. DOX+C/GP (doxorubicin in chitosan/β-glycerophosphate) was prepared to compare with LipDOX+C/GP (liposomal doxorubicin in chitosan/β-glycerophosphate hydrogel)...
September 20, 2016: European Journal of Pharmaceutical Sciences
Michael Peller, Linus Willerding, Simone Limmer, Martin Hossann, Olaf Dietrich, Michael Ingrisch, Ronald Sroka, Lars H Lindner
The efficacy of systemically applied, classical anti-cancer drugs is limited by insufficient selectivity to the tumor and the applicable dose is limited by side effects. Efficacy could be further improved by targeting of the drug to the tumor. Using thermosensitive liposomes (TSL) as a drug carrier, targeting is achieved by control of temperature in the target volume. In such an approach, effective local hyperthermia (40-43°C) (HT) of the tumor is considered essential but technically challenging. Thus, visualization of local heating and drug release using TSL is considered an important tool for further improvement...
September 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Laura Zorzetto, Paola Brambilla, Elena Marcello, Nora Bloise, Manuela De Gregori, Lorenzo Cobianchi, Andrea Peloso, Massimo Allegri, Livia Visai, Paola Petrini
Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades...
2016: International Journal of Nanomedicine
Yannan Nancy Dou, Michael Dunne, Huang Huang, Trevor Mckee, Martin C Chang, David A Jaffray, Christine Allen
Treatment efficacy of a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, was determined in xenograft models of non-small-cell lung carcinoma. The short-term impact of local hyperthermia (HT) on tumor morphology, microvessel density and local inflammatory response was also evaluated. The HTLC formulation in combination with local HT resulted in a significant advantage in therapeutic effect in comparison with free drug and a non-thermosensitive liposome formulation of CDDP (i...
November 2016: Journal of Drug Targeting
Azadeh Haeri, Lilia R C Pedrosa, Timo L M Ten Hagen, Simin Dadashzadeh, Gerben A Koning
Despite the advantages of liposomal drug delivery, the bioavailability of the chemotherapeutic drugs to tumor cells is limited by their slow release from nanocarriers and low drug permeability across cell membranes. Drug encapsulation into stealth thermosensitive liposomes can improve drug delivery to tumors by combining efficient accumulation at tumors and the active release of the payload following remote heat triggering. Short-chain sphingolipids are known to enhance cellular uptake of amphiphilic drugs...
April 2016: Journal of Biomedical Nanotechnology
Wen Lin, Xiangyang Xie, Yanfang Yang, Xudong Fu, Hong Liu, Yang Yang, Jianping Deng
To specifically deliver cytotoxic drug to tumor cells and enhance cellular uptake is the key for effective cancer therapy. In this paper, we described a novel drug targeting system, which is designed to combine features of biological (cell-penetrating peptides, CPPs) and physical (magnetic) drug targeting for use in the magnetic hyperthermia-triggered release. A doxorubicin-CPPs conjugate (DOX-CPPs) was loaded into thermosensitive magnetic liposomes (TSMLs) (DOX-CPPs/TSMLs), and in vitro DOX-CPPs thermosensitive release activity, anti-proliferation effect, in vivo targeted delivery as well as in vivo antitumor activity were determined...
November 2016: Drug Delivery
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