Mass transfer Linsitinib concentration equations describing the transport of drugs are

coded by using the User Defined Scalar (known as UDS). These equations are solved in conjunction with the continuity and momentum equations using numerical algorithms available in FLUENT. Spatial discretisation is performed by employing the second order UPWIND scheme, while pressure-velocity coupling is achieved by the SIMPLEC algorithm. The absolute criteria for residual tolerances for solutions of the Navier-Stokes equations and the drug transport equations are 1 × 10−5 and 1 × 10−8, respectively. The equations for the interstitial fluid flow are solved first to obtain a steady-state solution in the entire tumour and its Inhibitors,research,lifescience,medical surrounding normal tissues. The obtained pressure Inhibitors,research,lifescience,medical and velocity fields are then applied to the equations for drug transport. The second-order implicit backward Euler scheme is used for temporal discretisation, and a fixed time step size of 10 seconds is chosen, which is obtained after time-step sensitivity tests. 3. Results and Discussion The microenvironment in tumour and normal tissues plays an important role in determining the efficiency of liposome and drug transport. The interstitial fluid pressure (IFP) determines the drug exchange between interstitial fluid and blood plasma, as well as tumour and normal tissues. The mean Inhibitors,research,lifescience,medical IFP predicted in the tumour region is 1533Pa, which is almost identical to the value

reported Inhibitors,research,lifescience,medical by Baxter and Jain [15]. The mean IFP in the normal tissue is 41Pa. The spatial distribution of IFP in tumour and normal tissues is shown in Figure 3. It is clear that pressures in the tumour and normal tissues are at different levels, and a thin layer of steep pressure gradient exists at the interface between the two regions. Figure 3 Interstitial fluid pressure distribution in tumour and normal tissues. Liposome encapsulated doxorubicin concentration is a key parameter that determines the doxorubicin concentration in tumour cells. Shown in Figure

Inhibitors,research,lifescience,medical 4 are the predicted time courses of liposome encapsulated doxorubicin concentrations in blood plasma and interstitial space in tumour and normal tissues, for a total doxorubicin dose of 50mg/m2 encapsulated in thermosensitive liposomes. Figure 4 Liposome concentration in plasma and interstitial fluid as a function of time after start of treatment (dose = 50mg/m2). Liposome encapsulated doxorubicin is administrated into blood in a very Rolziracetam short duration, and its concentration in plasma decreases following an exponential decay function of time during the entire treatment period [13]. Its concentration in tumour increases rapidly in the initial stage after administration. This is because at this stage, the concentration in plasma is much higher than that in tumour, providing the driving force for liposome to pass through the vasculature wall and accumulate in tumour.