Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound

Negussie, Ayele H.; Yarmolenko, Pavel S.; Partanen, Ari; Ranjan, Ashish; Jacobs, Genevieve C.; Woods, David L.; Bryant, Henry L.; Thomasson, David; Dewhirst, Mark W.; Wood, Bradford J.; Dreher, Matthew R.

doi:10.3109/02656736.2010.528140

Cited by 152 publications

(133 citation statements)

References 51 publications

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“…Fabrication of DOX-loaded hyperthermia sensitive liposomes: Thermosensitive liposomes were prepared as described by Negussie et al[28,29], with slight changes. Briefly, dipalmitoyl phosphatidylcholine (DPPC), monostearoyl phosphatidylcholine (MSPC) and distearoyl phosphatidylethanolamine-poly(ethylene)glycol 2000 (DSPE-PEG2000) in a molar ratio of 85.3: 9.7: 5.0 were dissolved in chloroform and a lipid film was formed in a rotavapor under vacuum, at 40°C.…”

Section: Methodsmentioning

confidence: 99%

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Hyperthermia‐Induced Drug Delivery from Thermosensitive Liposomes Encapsulated in an Injectable Hydrogel for Local Chemotherapy

López-Noriega

Hastings

Ozbakir

et al. 2014

Adv Healthcare Materials

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One of the main challenges in cancer treatment is the administration of active doses of chemotherapeutic to a tumor site while minimizing severe side effects. On this basis, researchers have developed different materials for achieving both spatial and temporal effective release of the active molecule at the therapeutic target. [1][2][3][4] Among these materials, the locoregional administration of drug-loaded, in situ gelling hydrogels overcomes the pharmacokinetic restrictions of intravenous injection and effectively enhances the therapeutic ratio. [5,6] Following this principle, the present work describes the design of a composite material which enables a thermally triggered and localized release of a chemotherapeutic (doxorubicin), achievable through incorporation of drug-loaded thermosensitive liposomes in a thermoresponsive chitosan/β-glycerophosphate (C/β-GP) hydrogel for local treatment.Doxorubicin (DOX) is sequentially released from the gel by 1) passive diffusion of entrapped free drug and a small portion of drug-loaded liposomes, and 2) external thermal activation of the drug-loaded liposomes irreversibly trapped in the gel. The effect of this on-demand 2 scheduled dosing is assayed in vitro with human ovarian carcinoma cells, and is proposed as a way to challenge some of the compensatory mechanisms available to tumor cells. By reducing the exposure to sublethal doses of chemotherapeutic, the growth of cells with a short doubling time is inhibited while also potentially avoiding the development of drug resistance. [7][8][9] Our proposed approach combines the in situ gelation of thermoresponsive C/β-GP hydrogels and the on-demand release achievable using thermosensitive liposomes, with the aim of providing a localized, optimal delivery of chemotherapeutic. C/β-GP-based gelling systems have been widely studied because of their biocompatible and biodegradable properties. [10,11] However, a feature which makes these hydrogels especially attractive is that they can be formulated as a syringable solution at working temperatures that undergoes a gelation at body temperature, enabling a minimally invasive delivery and localized cohesion and release of encapsulated agents. Studies investigating intratumoral injections of anticancer drug-releasing C/β-GP hydrogels in vivo have shown encouraging results. [12] Lysolipid thermally sensitive liposomes (LTSLs) are bilayered spherical vesicles that rapidly change structure upon mild hyperthermia (41-43ºC), creating openings in the liposome which release the drug payload.[13]DOX can be efficiently loaded in LTSLs by the pH gradient method, [14] in which the creation of a transmembrane proton gradient induces the accumulation of the drug into the acidic interior of the liposome. This mechanism of drug uptake also allows a pH-sensitive release when the liposome is subjected to an acid pH, such as in the endosomal compartments after cell internalization.[15]The combination of C/β-GP hydrogels with DOX-loaded LTSLs gives rise to a homogeneous dispersion (Scheme 1A) that, up...

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Section: Methodsmentioning

confidence: 99%

“…Fabrication of DOX-loaded hyperthermia sensitive liposomes: Thermosensitive liposomes were prepared as described by Negussie et al [28,29], with slight changes. Preparation of chitosan/β-glycerophosphate gels: Preparation of thermoresponsive C/ β-GP gels has been described elsewhere [30].…”

Section: Methodsmentioning

confidence: 99%

Hyperthermia‐Induced Drug Delivery from Thermosensitive Liposomes Encapsulated in an Injectable Hydrogel for Local Chemotherapy

López-Noriega

Hastings

Ozbakir

et al. 2014

Adv Healthcare Materials

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“…The drugs loaded on temperature sensitive liposomes were rapidly released in the target region by thermal effects of ultrasound at physiologically temperatures as a result of heating to generate a transition of the phospholipid membrane from a gel to a fluid [68][69][70][71]. In addition, the PFC nanoparticles encapsulated doxorubicin in combination with RF ablation have been receiving clinical trials [69,72].…”

Section: The Machanism Of Pfc Nanoparticles For Ultrasound Theranostimentioning

confidence: 99%

Phase-transition Perfluorocarbon Nanoparticles for Ultrasound Molecular Imaging and Therapy

Xu¹,

Cao²,

Xu³

et al. 2015

Nano BioMed ENG

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Recently, the advances in perfluorocarbon nanoparticles have been introduced to expand the diagnostic and therapeutic capability of ultrasound molecular imaging, a non-invasive diagnostic imaging, which passed from robust anatomical presentation to detection of physiological processes and recognition of specific tissue epitopes at the cellular level. The good properties of perfluorocarbon nanoparticles, such as nontoxicity, small size, phase-shift capability, etc., have been resulted in tremendous potential prospects in clinical application. Herein, this review focuses on the mechanisms of perfluorocarbon nanoparticles in terms of phase transition and ultrasonic theranostic. And the potential applications of perfluorocarbon nanoparticles in ultrasound medicine are also discussed.

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“…Dedicated hybrid systems have already been introduced into clinical applications. 15,78,79 Localized drug release from TSL has been demonstrated in rodents, 55,80 and nonrodents, [81][82][83] using MRI for the control of hyperthermia. Beyond controlling the volume of heating, encapsulation of MRI contrast agents in TSL formulations allows additional characterization of the drug delivery only accessible in humans when using MRI.…”

Section: Thermosensitive Liposomes For Mri-guided Drug Deliverymentioning

confidence: 99%

“…Paramagnetic gadolinium chelates 54,82,[84][85][86] and manganese ions [87][88][89][90] are typical MRI-active contrast agents for encapsulation in TSL formulations ( Table 1). The nuclear magnetic resonance of water protons is the primary origin of MRI signal and not the contrast agent itself.…”

Section: Signal Mechanismmentioning

confidence: 99%

Thermosensitive liposomal drug delivery systems: state of the art review

Kneidl¹,

Peller²,

Winter³

et al. 2014

IJN

148

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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. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.

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Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound

Cited by 152 publications

References 51 publications

Hyperthermia‐Induced Drug Delivery from Thermosensitive Liposomes Encapsulated in an Injectable Hydrogel for Local Chemotherapy

Hyperthermia‐Induced Drug Delivery from Thermosensitive Liposomes Encapsulated in an Injectable Hydrogel for Local Chemotherapy

Phase-transition Perfluorocarbon Nanoparticles for Ultrasound Molecular Imaging and Therapy

Thermosensitive liposomal drug delivery systems: state of the art review

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