Transport of Liposome Encapsulated Drugs in Voxelized Computational Model of Brain Tumors

Introduction: Cancer is one of the leading causes of death all over the world. Various treatment strategies are now a days used for treatment of cancers such as chemotherapy, radiotherapy and surgical removal. Liposome... [ view full abstract ]

Introduction:
Cancer is one of the leading causes of death all over the world. Various treatment strategies are now a days used for treatment of cancers such as chemotherapy, radiotherapy and surgical removal. Liposome mediated drug delivery has emerged as an excellent anticancer therapy due to its ability to deliver drugs at site of action and reducing the chances of side effects to the healthy tissues. Computational modelling provides us a non-invasive approach to predict the transport mechanism of liposomes to tumor site and their accumulation within tumor tissues. Aim of this study is to perform computer simulations to qualitatively and quantitatively analyze the deposition of liposomes in human brain tumors. Additionally, the size effect is incorporated by considering stealth (PEG encapsulated doxorubicin) and conventional liposomes. Their accumulation results are compared with the free drug (doxorubicin).
Methods:
In this study computational fluid dynamics has been used to develop a voxelized model based on DCE-MRI. Complete analogy is maintained between MRI slice and CFD slice by assigning all the variables voxelwise. All the fluid flow and solute transport equations have been simulated to predict the transport of liposomes to tumor site. To the best of our knowledge this is the first study to predict the transport of liposomes in realistic heterogeneous vasculature of tumors computationally.
Results and Discussions:
Simulation has been performed for 48 hours. Results indicate that stealth liposomes accumulate more and remain for longer period of time in tumors as compared to conventional liposomes and free drug. Stealth liposome concentration has been estimated approximately 20 fold more than that of free drug and it remains in the tumor tissue for longer period as compared to conventional liposomes and free drug. These values have been validated with those in literature. Reason behind stealth liposome more accumulation in tumors is their slower plasma and higher vascular clearance. This increases the therapeutic effect of drug and also their probability of killing tumor cells due to long drug exposure. This computational study potentially enables medical professionals to forecast the overall effectiveness of the drug and optimize treatment strategy for each patient.