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Thermosensitive liposomes

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...
June 16, 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...
June 7, 2016: Drug Delivery
Monira M Rageh, Medhat W Shafaa, Mona R Elhefnawy, Mohamed S El-Nagdy
Nanoscales thermosensitive liposomes (TSL) composed of synthetic lipids (dipalmitoylphosphatidylcholine, and distearoylphosphatidylcholine), were used for doxorubicin encapsulation with 70% encapsulated efficiency. The liposomes were characterized by dynamic light scattering, transmission electron microscopy and turbidity method. Additionally, the liposomes exhibited a significant release of doxorubicin (Dox) by 60% within 5 min at 42°C. To assess the therapeutic efficacy of Dox in combination with hyperthermia, Dox free and encapsulated TSL were administered directly to Ehrlich tumor bearing mice at 1 mg/kg dose...
July 2016: General Physiology and Biophysics
Yanfang Yang, Yang Yang, Xiangyang Xie, Xueqing Xu, Xuejun Xia, Hongliang Wang, Lin Li, Wujun Dong, Panpan Ma, Yuling Liu
Small interfering RNA (siRNA) offers a new and potential therapeutic strategy for tackling many diseases at the molecular level. Recently, cell-penetrating peptides (CPPs) conjugated with siRNA via disulfide-bonds (designated as siRNA-CPPs) were reported to form glutathione-sensitive carriers. However, non-cell specificity, CPPs degradation and the unwanted reduction of siRNA-CPPs before reaching the targeted tissue in vivo hampered the development of siRNA-CPPs. Herein, utilizing the dual stimulus of hyperthermia and the intracellular redox environment, we devised a thermosensitive liposome (TSL) containing an Asparagine-Glycine-Arginine (NGR) peptide and reducible siRNA-CPPs for tumor-specific siRNA transfection (siRNA-CPPs/NGR-TSL), in which siRNA-CPPs were "caged" in NGR-TSL to overcome their limitations in vivo...
June 15, 2016: International Journal of Pharmaceutics
H O'Neill, C Herron, C Hastings, A Lopez-Noriega, H M Kelly, F J O'Brien, E Ruiz-Hernandez, G P Duffy
No abstract text is available yet for this article.
September 10, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Hyun Ryoung Kim, Dong Gil You, Sang-Jun Park, Kyu-Sil Choi, Wooram Um, Jae-Hun Kim, Jae Hyung Park, Young-Sun Kim
Monitoring of drug release from a heat-activated liposome carrier provides an opportunity for real-time control of drug delivery and allows prediction of the therapeutic effect. We have developed short-chain elastin-like polypeptide-incorporating thermosensitive liposomes (STLs). Here, we report the development of STL encapsulating gadobenate dimeglumine (Gd-BOPTA), a MRI contrast agent, and doxorubicin (Dox) (Gd-Dox-STL). The Dox release profile from Gd-Dox-STL was comparable to Gd-Dox-LTSL; however, the serum stability of Gd-Dox-STL was much higher than Gd-Dox-LTSL...
May 2, 2016: Molecular Pharmaceutics
Xiaoxiao Tan, Xiaojuan Pang, Mingzhu Lei, Man Ma, Fang Guo, Jinping Wang, Meng Yu, Fengping Tan, Nan Li
The therapeutic effectiveness of photodynamic therapy (PDT) was hampered by the poor water solubility and instability in physiological conditions of the photosensitizers. Here, we designed folate conjugated thermosensitive liposomes (TSL) as the nanocarrier to improve the solubility, stability and biocompatibility of photosensitizer Chlorin e6 (Ce6). Based on the photothermal effect, we combined copper sulfide (CuS) as the photothermal agent to realize heat-triggered Ce6 release as well as synergistic effect of photothermal and photodynamic therapy...
April 30, 2016: International Journal of Pharmaceutics
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