Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid-based thermosensitive liposomes

Sadeghi, Negar; Deckers, Roel; Ozbakir, Burcin; Akthar, Sohail; Kok, Robbert J.; Lammers, Twan; Storm, Gert

doi:10.1016/j.ijpharm.2017.11.002

Cited by 34 publications

(26 citation statements)

References 31 publications

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“…This was followed by a sudden increase of fluorescence intensity at temperatures ≥41 °C, with more than 80 % of the encapsulated drug released in 2 min at 43 °C. iTSL-DOX demonstrated almost identical release profiles in buffer and serum-like conditions ( Figure 1B) which bodes well for its use in vivo [27]. This thermally-induced drug release aligns well with liquid-phase DSC thermograms collected for iTSL-NO-DOX (without loaded doxorubicin) and iTSL-DOX ( Figure 1C-D).…”

Section: Thermally-induced Doxorubicin Releasesupporting

confidence: 75%

MR-labelled liposomes and focused ultrasound for spatiotemporally controlled drug release in triple negative breast cancers in mice

et al. 2021

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Rationale: Image-guided, triggerable, drug delivery systems allow for precisely placed and highly localised anti-cancer treatment. They contain labels for spatial mapping and tissue uptake tracking, providing key location and timing information for the application of an external stimulus to trigger drug release. High Intensity Focused Ultrasound (HIFU or FUS) is a non-invasive approach for treating small tissue volumes and is particularly effective at inducing drug release from thermosensitive nanocarriers. Here, we present a novel MR-imageable thermosensitive liposome (iTSL) for drug delivery to triple-negative breast cancers (TNBC). Methods: A macrocyclic gadolinium-based Magnetic Resonance Imaging (MRI) contrast agent was covalently linked to a lipid. This was incorporated at 30 mol% into the lipid bilayer of a thermosensitive liposome that was also encapsulating doxorubicin. The resulting iTSL-DOX formulation was assessed for physical and chemical properties, storage stability, leakage of gadolinium or doxorubicin, and thermal-or FUS-induced drug release. Its effect on MRI relaxation time was tested in phantoms. Mice with tumours were used for studies to assess both tumour distribution and contrast enhancement over time. A lipid-conjugated near-infrared fluorescence (NIRF) probe was also included in the liposome to facilitate the real time monitoring of iTSL distribution and drug release in tumours by NIRF bioimaging. TNBC (MDA-MB-231) tumour-bearing mice were then used to demonstrate the efficacy at retarding tumour growth and increasing survival. Results: iTSL-DOX provided rapid FUS-induced drug release that was dependent on the acoustic power applied. It was otherwise found to be stable, with minimum leakage of drug and gadolinium into buffers or under challenging conditions. In contrast to the usually suggested longer FUS treatment we identified that brief (~3 min) FUS significantly enhanced iTSL-DOX uptake to a targeted tumour and triggered near-total release of encapsulated doxorubicin, causing significant growth inhibition in the TNBC mouse model. A distinct reduction in the tumours' average T1 relaxation times was attributed to the iTSL accumulation. Conclusions: We demonstrate that tracking iTSL in tumours using MRI assists the application of FUS for precise drug release and therapy.

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Section: Thermally-induced Doxorubicin Releasesupporting

confidence: 75%

MR-labelled liposomes and focused ultrasound for spatiotemporally controlled drug release in triple negative breast cancers in mice

et al. 2021

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“…During the 100 h accumulative drug release study, only 30% of the DOX was released from Lip5. This outcome might be due to the high cholesterol content causing an increase in the order of the lipid membrane and consequently preventing the leakage of DOX from the preparation 21 . The in vitro drug release profiles suggested that the drug-loaded liposomes might retain most of the encapsulated drug during the penetration process.…”

Section: Resultsmentioning

confidence: 99%

“…Cholesterol, a crucial constituent of liposomes, has not received adequate attention. In addition to its well-known functions in liposomes, such as the enhancement in membrane ordering 20 and liposomal stability 21 , cholesterol also has significant influence on the rigidity of liposomes 22 and can affect liposomal cellular uptake 23 . Furthermore, it is more convenient and biocompatible to change the cholesterol content of liposomes, compared to liposomal surface modifications and environmentally sensitive modifications.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect

Miao

et al. 2019

Acta Pharmaceutica Sinica B

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Recently, liposomes have been widely used in cancer therapeutics, but their anti-tumor effects are suboptimal due to limited tumor penetration. To solve this problem, researchers have made significant efforts to optimize liposomal diameters and potentials, but little attention has been paid to liposomal membrane rigidity. Herein, we sought to demonstrate the effects of cholesterol-tuned liposomal membrane rigidity on tumor penetration and anti-tumor effects. In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[methoxy(polyethylene glycol)-2000] (DSPE-PEG 2000 ) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with moderate rigidity leading to improved diffusion. Next, the in vitro tumor penetration and the in vivo anti-tumor effects were analyzed. The results showed that liposomes with moderate rigidity gained excellent tumor penetration and enhanced anti-tumor effects. These findings illustrate a feasible and effective way to improve tumor penetration and therapeutic efficacy of liposomes by changing the cholesterol content, and highlight the importance of liposomal membrane rigidity.

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“…This reduces liposomal uptake by the reticuloendothelial system. Moreover, the fusogenic features of some lipids (such as DPPG) in the liposomal membrane are reported to improve the ability of liposomes to cross the cancer cell membrane [ 51 , 52 ].…”

Section: Liposomal Photosensitizer Formulations For Tumor Photodynamic Therapymentioning

confidence: 99%

Liposome Photosensitizer Formulations for Effective Cancer Photodynamic Therapy

2021

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Photodynamic therapy (PDT) is a promising non-invasive strategy in the fight against that which circumvents the systemic toxic effects of chemotherapeutics. It relies on photosensitizers (PSs), which are photoactivated by light irradiation and interaction with molecular oxygen. This generates highly reactive oxygen species (such as 1O2, H2O2, O2, ·OH), which kill cancer cells by necrosis or apoptosis. Despite the promising effects of PDT in cancer treatment, it still suffers from several shortcomings, such as poor biodistribution of hydrophobic PSs, low cellular uptake, and low efficacy in treating bulky or deep tumors. Hence, various nanoplatforms have been developed to increase PDT treatment effectiveness and minimize off-target adverse effects. Liposomes showed great potential in accommodating different PSs, chemotherapeutic drugs, and other therapeutically active molecules. Here, we review the state-of-the-art in encapsulating PSs alone or combined with other chemotherapeutic drugs into liposomes for effective tumor PDT.

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Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid-based thermosensitive liposomes

Cited by 34 publications

References 31 publications

MR-labelled liposomes and focused ultrasound for spatiotemporally controlled drug release in triple negative breast cancers in mice

MR-labelled liposomes and focused ultrasound for spatiotemporally controlled drug release in triple negative breast cancers in mice

Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect

Liposome Photosensitizer Formulations for Effective Cancer Photodynamic Therapy

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