ArticleInternational journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group2015
Temperature-sensitive liposome-mediated delivery of thrombolytic agents.
Article in International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 33 citations in OpenAlex.
- Overview of Venous Thromboembolism and Emerging Therapeutic Technologies Based on Nanocarriers-Mediated Drug Delivery Systems.Molecules (Basel, Switzerland) · 2024Review
- Functional candesartan loaded lipid nanoparticles for the control of diabetes-associated stroke: In vitroInternational journal of pharmaceutics: X · 2024Article
- Innovations in Breaking Barriers: Liposomes as Near-Perfect Drug Carriers in Ischemic Stroke Therapy.International journal of nanomedicine · 2024Review
- Review
- The Optimized Delivery of Triterpenes by Liposomal Nanoformulations: Overcoming the Challenges.International journal of molecular sciences · 2022Review
- Development and Testing of Thrombolytics in Stroke.Journal of stroke · 2021Review
- Thrombolytic Agents: Nanocarriers in Controlled Release.Small (Weinheim an der Bergstrasse, Germany) · 2020Review
- Ultrasound-Sensitive Liposomes for Triggered Macromolecular Drug Delivery: Formulation andFrontiers in pharmacology · 2019Article
- Localized delivery of therapeutic doxorubicin dose across the canine blood-brain barrier with hyperthermia and temperature sensitive liposomes.Drug delivery · 2018Article
- The evolution of recombinant thrombolytics: Current status and future directions.Bioengineered · 2017Article
- Encapsulation of eptifibatide in RGD-modified nanoliposomes improves platelet aggregation inhibitory activity.Journal of thrombosis and thrombolysis · 2017Article
- Advanced Functional Nanomaterials for Theranostics.Advanced functional materials · 2017Article
- Structure and Function of Trypsin-Loaded Fibrinolytic Liposomes.BioMed research international · 2017Article
- Radiosensitivity in HeLa cervical cancer cells overexpressing glutathione S-transferase π 1.Oncology letters · 2015Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundClinical efficacy of thrombolytic drugs is limited by lack of specific delivery and requires large therapeutic doses which increase toxicity. Encapsulating these drugs in temperature-sensitive liposomes and applying hyperthermia to deliver thrombolytic agents locally to thrombus might theoretically favourably alter the therapeutic window. The objectives of this study were to formulate liposomes encapsulating thrombolytics and assess thrombolytic activity following hyperthermia.
methodsThree liposome formulations were investigated: temperature-sensitive liposome (TSL, DPPC:DSPE-PEG2000 (mol% 95:5)), low temperature-sensitive liposome (LTSL, DPPC:MSPC:DSPE-PEG2000 (mol% 85.3:9.7:5)), and traditional temperature-sensitive liposome (TTSL, DPPC:HSPC:Chol:DSPE-PEG2000 (mol% 55:25:15:5)). To characterise temperature-dependent release of high molecular weight cargo from each formulation, fluorescein-conjugated dextrans (70 kDa) were loaded and release was quantified via spectrophotometry. Staphylokinase (SAK), urokinase, and tissue-type plasminogen activator were also loaded individually into each liposome formulation. Leakage at 37 °C and release at 38-44 °C were quantified via chromogenic enzymatic activity assay. Clot lysis was evaluated by measuring mass of blood clots before and after thrombolytic liposome treatment.
resultsThe LTSL formulation had optimal release characteristics with maximum release at 41.3 °C. Release of dextrans from LTSLs was observed to be 11.5 ± 1.5%, 79.7 ± 1.6%, and 93.6 ± 3.7% after 15 min in plasma at 37°, 39°, and 41.3 °C, respectively. The SAK LTSL had the highest release/leakage ratio and demonstrated greater clot lysis.
conclusionsThe SAK LTSL achieves significant clot lysis in vitro. When combined with local hyperthermia, the SAK LTSL potentially produces sufficient thrombolysis while minimising systemic side effects.
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