The intra-tumoral relationship between microcirculation, interstitial fluid pressure and liposome accumulation

Stapleton, Shawn; Milosevic, Michael; Tannock, Ian F.; Allen, Christine; Jaffray, David A.

doi:10.1016/j.jconrel.2015.06.008

Cited by 68 publications

(61 citation statements)

References 39 publications

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“…Our result has been confirmed by experimental studies of drug distribution using large drugs such as micelles [60, 61], nanoprobes [62] and liposomes [59, 63–66] in which peripheral accumulation is observed.…”

Section: Discussionsupporting

confidence: 79%

“…It also shows us that IFP and drug accumulation are not always correlated, rather the maximum accumulation is achieved through the complex interplay between IFP, vessel density and leakiness. Current research by [63] also supports this view; in their mouse study, they point out that IFP is correlated with perfusion, perfusion is correlated with accumulation and the relationship between IFP and liposome accumulation is limited.…”

Section: Discussionmentioning

confidence: 85%

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Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy

et al. 2017

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Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 85%

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy

et al. 2017

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“…Recently, Stapleton et al reported a technique which will allow the measurement of spatial IFP [56]. These measurements use a robotic needle placement device guided under microcomputed tomography (CT) (Figure 2).…”

Section: Current Strategiesmentioning

confidence: 99%

“…IFP measurements were higher in the tumor center than at the tumor periphery. Reproduced with permission from [56]. …”

Section: Figurementioning

confidence: 99%

Strategies for improving the intratumoral distribution of liposomal drugs in cancer therapy

Goins

Phillips

Bao

2016

Expert Opinion on Drug Delivery

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Introduction A major limitation of current liposomal cancer therapies is the inability of liposome therapeutics to penetrate throughout the entire tumor mass. This inhomogeneous distribution of liposome therapeutics within the tumor has been linked to treatment failure and drug resistance. Both liposome particle transport properties and tumor microenvironment characteristics contribute to this challenge in cancer therapy. This limitation is relevant to both intravenously and intratumorally administered liposome therapeutics. Areas covered Strategies to improve the intratumoral distribution of liposome therapeutics are described. Combination therapies of intravenous liposome therapeutics with pharmacologic agents modulating abnormal tumor vasculature, interstitial fluid pressure, extracellular matrix components, and tumor associated macrophages are discussed. Combination therapies using external stimuli (hyperthermia, radiofrequency ablation, magnetic field, radiation, and ultrasound) with intravenous liposome therapeutics are discussed. Intratumoral convection-enhanced delivery (CED) of liposomal therapeutics is reviewed. Expert opinion Optimization of the combination therapies and drug delivery protocols are necessary. Further research should be conducted in appropriate cancer types with consideration of physiochemical features of liposomes and their timing sequence. More investigation of the role of tumor associated macrophages in intratumoral distribution is warranted. Intratumoral infusion of liposomes using CED is a promising approach to improve their distribution within the tumor mass.

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“…Therefore, imaging of tumor perfusion and oxygenation may be used to predict nanoparticle distribution and localization, as a surrogate to measuring nanoparticle delivery directly. Perfusion imaging with CT has shown a strong correlation between tumor perfusion and liposome distribution in several preclinical tumor models [48,49]. This section addresses how imaging tools may be applied to assess tumor metabolism, perfusion, diffusion of water, blood oxygenation, and distribution of nanoparticle contrast agents using MRI-based imaging.…”

Section: Imaging Modalities and Molecular Imaging Tracers For Patientmentioning

confidence: 99%

Integration of imaging into clinical practice to assess the delivery and performance of macromolecular and nanotechnology-based oncology therapies

Spence

Souza

Dou

et al. 2015

Journal of Controlled Release

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The intra-tumoral relationship between microcirculation, interstitial fluid pressure and liposome accumulation

Cited by 68 publications

References 39 publications

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy

Strategies for improving the intratumoral distribution of liposomal drugs in cancer therapy

Integration of imaging into clinical practice to assess the delivery and performance of macromolecular and nanotechnology-based oncology therapies

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