Convection enhanced delivery of liposome encapsulated doxorubicin for brain tumour therapy

Zhan, Wenbo; Wang, Chi-Hwa

doi:10.1016/j.jconrel.2018.07.006

Cited by 63 publications

(41 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, the adopted models have been validated separately by other researchers for HIFU acoustic field (Sheu et al 2011) and HIFU-induced temperature variation (Staruch et al 2011). The macroscopic transport model has been shown to be able to provide qualitative predictions on drug transport and accumulation in solid tumours (Bhandari et al 2017;Zhan and Wang 2018). Given the complexities involved in the drug delivery process, more rigorous validation studies are needed in the future.…”

Section: Discussionmentioning

confidence: 99%

Towards a multiphysics modelling framework for thermosensitive liposomal drug delivery to solid tumour combined with focused ultrasound hyperthermia

Zhan

Gedroyc

2019

Biophys Rep

Self Cite

View full text Add to dashboard Cite

Systemic toxicity and insufficient drug accumulation at the tumour site are main barriers in chemotherapy. Thermosensitive liposomes (TSL) combined with high intensity focused ultrasound (HIFU) has emerged as a potential solution to overcome these barriers through targeted drug delivery and localised release. Owing to the multiple physical and biochemical processes involved in this combination therapy, mathematical modelling becomes an indispensable tool for detailed analysis of the transport processes and prediction of tumour drug uptake. To this end, a multiphysics model has been developed to simulate the transport of chemotherapy drugs delivered through a combined HIFU-TSL system. All key delivery processes are considered in the model; these include interstitial fluid flow, HIFU acoustics, bioheat transfer, drug release and transport, as well as tumour drug uptake. The capability of the model is demonstrated through its application to a 2-D prostate tumour model reconstructed from magnetic resonance images. Our results not only demonstrate the feasibility of the model to simulate this combination therapy, but also confirm the advantage of HIFU-TSL drug delivery system with enhancement of drug accumulation in tumour regions and reduction of drug availability in normal tissue. This multiphysics modelling framework can serve as a useful tool to assist in the design of HIFU-TSL drug delivery systems and treatment regimen for improved anticancer efficacy.

show abstract

Section: Discussionmentioning

confidence: 99%

Towards a multiphysics modelling framework for thermosensitive liposomal drug delivery to solid tumour combined with focused ultrasound hyperthermia

Zhan

Gedroyc

2019

Biophys Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Model-predicted drug transport profiles were well fit to the measurements reported from ex vivo experiments, with the coefficient of multiple determination reaching 0.83 [80]. Although comparisons to animal experiments remain qualitative for small molecular drugs [81,82], the prediction accuracy can be largely improved for the drug vehicles in nanoscale [83]. Therefore, since this study was focused on drug transport rather than model development, the work of model validation was not duplicated here.…”

Section: Discussionmentioning

confidence: 95%

Effects of Focused-Ultrasound-and-Microbubble-Induced Blood-Brain Barrier Disruption on Drug Transport under Liposome-Mediated Delivery in Brain Tumour: A Pilot Numerical Simulation Study

Zhan

2020

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Focused ultrasound (FUS) coupled with microbubbles (MB) has been found to be a promising approach to disrupt the blood-brain barrier (BBB). However, how this disruption affects drug transport remains unclear. In this study, drug transport in combination therapy of liposomes and FUS-MB-induced BBB disruption (BBBD) was investigated based on a multiphysics model. A realistic 3D brain tumour model extracted from MR images was applied. The results demonstrated the advantage of liposomes compared to free doxorubicin injection in further improving treatment when the BBB is opened under the same delivery conditions using burst sonication. This improvement was mainly due to the BBBD-enhanced transvascular transport of free doxorubicin and the sustainable supply of the drug by long-circulating liposomes. Treatment efficacy can be improved in different ways. Disrupting the BBB simultaneously with liposome bolus injection enables more free drug molecules to cross the vessel wall, while prolonging the BBBD duration could accelerate liposome transvascular transport for more effective drug release. However, the drug release rate needs to be well controlled to balance the trade-off among drug release, transvascular exchange and elimination. The results obtained in this study could provide suggestions for the future optimisation of this FUS-MB–liposome combination therapy against brain cancer.

show abstract

“…Some of these nanosystems have been explored as glioblastoma therapeutics. Several studies have reported the use of liposomal formulations to deliver anti-cancer drugs, such as methotrexate, 5-fluorouracil, paclitaxel, erlotinib and doxorubicin [42][43][44][45][46][47]. Liposomes with sizes smaller than~200 nm have the capacity to cross the BBB [48][49][50][51].…”

Section: Lipid-based Nanosystemsmentioning

confidence: 99%

“…The most commonly explored are the hydrolysable (enzymatic mediated or hydrolysis) ester bonds, such as in the case of the commonly used PLGA, of which the degradation products (lactic acid and glycolic acid) are naturally present in the body and, therefore, it is fully biocompatible [42,43]. PCL is another biodegradable polyester which has a slow degradation process [44].…”

Section: Polymeric Nanosystemsmentioning

confidence: 99%

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

et al. 2020

View full text Add to dashboard Cite

Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.

show abstract

Convection enhanced delivery of liposome encapsulated doxorubicin for brain tumour therapy

Cited by 63 publications

References 100 publications

Towards a multiphysics modelling framework for thermosensitive liposomal drug delivery to solid tumour combined with focused ultrasound hyperthermia

Towards a multiphysics modelling framework for thermosensitive liposomal drug delivery to solid tumour combined with focused ultrasound hyperthermia

Effects of Focused-Ultrasound-and-Microbubble-Induced Blood-Brain Barrier Disruption on Drug Transport under Liposome-Mediated Delivery in Brain Tumour: A Pilot Numerical Simulation Study

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Contact Info

Product

Resources

About