0. 2.6.3. Liposome Release Rate (krel ) Thermosensitive liposome is designed to release its contents rapidly on heating [6]. The release rate varies according to the composition of liposome, its preparation procedure, and heating temperature [45]. The relation between percentage release and exposure time is found to follow the first-order kinetics expressed as [46] %R(t)=Rc(1−e−krel⁡t), (30) where %R(t)

is the percentage of drug released at exposure time t; Rc is the total percentage of drug released at a given heating temperature. This Inhibitors,research,lifescience,medical equation is used to fit the experimental data obtained at 42°C [45]. From the best fitting curve (shown in Figure 2) obtained by using nonlinear least-squares method, the release rate is found to be 0.0078. At normal Inhibitors,research,lifescience,medical physiological

temperature of 37°C, there should be no release; hence the release rate at 37°C is assumed to be zero. Figure 2 Liposome release rate at 42°C. 2.6.4. Plasma Pharmacokinetics (1) Direct Continuous Infusion. The doxorubicin concentration in blood plasma is modelled as an exponential decay function of time. Inhibitors,research,lifescience,medical The form of equation depends on the infusion mode. For continuous infusion, a triexponential decay function is assumed based on the plasma pharmacokinetics of doxorubicin: Cv=DT[(Aα(1−e−αt)+Bβ(1−e−βt)+Cγ(1−e−γt))]                    (t

Release. The liposome encapsulated doxorubicin concentration in blood plasma is found to follow a 2-exponential decaying function of time [13], written as Clp=A1e−k1t+A2e−k2t, (33) where heptaminol A1 and A2 are compartment parameters, and k1 and k2 are compartment clearance rates. 2.7. Boundary Conditions Because the time scale for the simulation is assumed to be short enough to ignore the growth of tumour and normal tissues, the interface between the tumour and normal tissue as well as the outer Cyclopamine concentration surface of normal tissue are fixed. The interface between the tumour and normal tissues is treated as an internal boundary where all variables are continuous. The relative pressure at the outer surface of normal tissues is assumed to be constant at 0Pa, where zero flux of drug is also specified. 2.8.