Systemic anti-tumour effects of local thermally sensitive liposome therapy

Viglianti, Benjamin L.; Dewhirst, Mark W.; Boruta, Richard J.; Park, Ji Young; Landon, Chelsea D.; Fontanella, Andrew N.; Guo, Jing; Manzoor, Ashley A.; Hofmann, Christina L.; Palmer, Gregory M.

doi:10.3109/02656736.2014.944587

Cited by 23 publications

(18 citation statements)

References 27 publications

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“…Viglianti, et al, tested whether doxorubicin-LTSL had systemic effects by performing experiments with mice that had two flank tumors: one was heated and the other was not. Antitumor effects were observed in both tumors (15). These results lend credence to the concept of using doxorubicin-LTSL with hyperthermia to a primary tumor, as some level of systemic antitumor effect is expected.…”

supporting

confidence: 67%

Thermally enhanced liposomal drug delivery

Dewhirst¹,

Lee²

2015

AACR Education book

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Background The purpose of this article is to review the concept of using heat to augment thermally sensitive liposomal drug delivery to tumors. If one loads a water soluble drug into the liposome below the lipid melting temperature, the drug will exhibit very slow release, which is dependent upon the solubility of the drug in lipid (1). A thermally sensitive liposome is designed to take advantage of changes in permeability when lipids melt. The mechanism leading to enhanced content release is thought to be related to opening of pores between plates of solid lipid, during the melting process (1). Details of the material science that leads to enhanced drug release will not be reviewed here; further details can be found in other reports (1-4). Historical Perspective Milton Yatvin was the first to use hyperthermia with drug loaded thermally sensitive liposomes to enhance drug delivery to tumors (5, 6), but some of the performance characteristics of this liposome were not optimized. Gaber, et al., examined liposomal accumulation and drug release from a pegylated version of the Yatvin liposome (7). Hyperthermia augmented liposome accumulation and drug release in tumors at 42-45 C, but the liposome did not fully release drug and the drug release kinetics were relatively slow (8) (Fig. 1). The slow release was particularly problematic because a liposome would pass through the vasculature of a tumor well before it released drug. To more efficiently capture released drug within the heated tumor, a liposome with faster drug release was sought. Drs. Dewhirst and Needham collaborated in the development of a temperature sensitive liposome that releases drug at a lower temperature (phase transition ¼ 41.3 C) (9, 10). Upon reaching its transition temperature, doxorubicin was nearly completely released in less than 20s (10). This formulation resulted in 25-30 and fivefold increase in drug delivery to a heated volume vs. free drug or non-thermally sensitive liposomes containing doxorubicin, respectively (11). Several other liposomal formulations have been reported that also exhibit rapid drug release between 41-42 C (3, 4, 12, 13). The acronym "LTSL," which stands for "lowtemperature sensitive liposome" is a generic term for this type of formulation. Drug Delivery Characteristics of LTSL and Clinical Implications Manzoor and Lindner, et al., used skin-fold window chambers to prove that drug delivery with LTSLs was purely the result of intravascular drug release in the heated tissue (14) (Fig. 2). Thermally mediated drug delivery to a local tumor has advantages and disadvantages, however. For example, it is difficult to justify giving neoadjuvant doxorubicin-LTSL to a woman with

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confidence: 67%

Thermally enhanced liposomal drug delivery

Dewhirst¹,

Lee²

2015

AACR Education book

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“…45 In fact, Thermodox, a lysolipid- containing thermosensitive liposome encapsulating doxorubicin, is in phase III clinical trials for the treatment of primary liver cancer. 46,47 Similarly, we envision that heat may be used to trigger the release of cargo from DMSs.…”

Section: Discussionmentioning

confidence: 99%

Dendrimersomes Exhibit Lamellar-to-Sponge Phase Transitions

et al. 2018

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Lamellar to nonlamellar membrane shape transitions play essential roles in key cellular processes, such as membrane fusion and fission, and occur in response to external stimuli, including drug treatment and heat. A subset of these transitions can be modeled by means of thermally inducible amphiphile assemblies. We previously reported on mixtures of hydrogenated, fluorinated, and hybrid Janus dendrimers (JDs) that self-assemble into complex dendrimersomes (DMSs), including dumbbells, and serve as promising models for understanding the complexity of biological membranes. Here we show, by means of a variety of complementary techniques, that DMSs formed by single JDs or by mixtures of JDs undergo a thermally induced lamellar-to-sponge transition. Consistent with the formation of a three- dimensional bilayer network, we show that DMSs become more permeable to water-soluble fluorophores after transitioning to the sponge phase. These DMSs may be useful not only in modeling isotropic membrane rearrangements of biological systems but also in drug delivery since nonlamellar delivery vehicles can promote endosomal disruption and cargo release.

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“…Via a range of effects, hyperthermia boosts the immune system to increase antitumour efficacy [86][87][88][89][90][91]. These effects may extend to tumour-bearing areas that are not effectively heated, via abscopal immune mediated effects [92].…”

Section: Discussionmentioning

confidence: 99%

Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer

Heijden

Dewhirst

2016

International Journal of Hyperthermia

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Non-muscle-invasive bladder cancer is a challenging disease, even given its superficial nature. It is prone to multiple recurrences and progression to muscle-invasive cancer. These features of this disease contribute significantly to reduced quality of life as well as creating significant morbidity and even mortality. Randomised trials demonstrate that when hyperthermia is added to conventional mitomycin-C treatment that local control rates and progression-free survival are substantially improved. In this review we consider how hyperthermia can exert such beneficial effects. Some of the mechanisms presented are theoretical, while others are facts. It is hoped that this review will contribute rationale for further examination of mechanisms, because an understanding of such mechanisms may lead to even better chemotherapeutic approaches, as well as potential biomarkers for predicting and monitoring treatment success.ARTICLE HISTORY

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Systemic anti-tumour effects of local thermally sensitive liposome therapy

Cited by 23 publications

References 27 publications

Thermally enhanced liposomal drug delivery

Thermally enhanced liposomal drug delivery

Dendrimersomes Exhibit Lamellar-to-Sponge Phase Transitions

Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer

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