Next, the initial release rate (at t = 0) is used to estimate kS. Last, koff that determines the kinetics of the sustained release is calculated. These estimated parameters (i.e., ΔG, kS, koff) are used as the initial input in Matlab codes to refine the estimations using an optimization Alvespimycin research buy method. The properties of the parameter estimates, such as mean and standard deviation, are assessed using bootstrap sampling [28], as detailed Inhibitors,research,lifescience,medical in Section 3.5. 3.2. Drug Release from Liposomes and Nanocapsules Liposomes and lipid nanocapsules (LNC) are among drug delivery systems that first made their way to clinical applications [5]. The bilayered structure of liposomes enables the encapsulation of hydrophilic

and lipophilic drug in their interior aqueous compartments (Figure 1(b)) and in the lipid bilayers (Figure 1(c)), respectively [32]. However, liposomes can be easily trapped by the reticuloendothelial system (RES), leading to rapid removal from circulation [33]. A hydrophilic barrier, often formed by polyethylene glycol (PEG) derivatives, Inhibitors,research,lifescience,medical may be created to protect liposomes, avoiding their uptake Inhibitors,research,lifescience,medical by RES [34]. PEGylation of liposomes increased their circulation half-times of about 30 minutes to 5 hours nearly two decades ago [34] to around 10 hours

recently [35], enhancing their spontaneous accumulation in solid tumors [34, 36]. Efforts to control release kinetics made it possible to deplete encapsulated drugs in a time comparable to or longer than the circulation time of liposomes [25, 26]. Here, we simulate drug release Inhibitors,research,lifescience,medical from liposomes and LNC at different time scales (Figures 3(a)–3(d)) and from polymeric

nanocapsules (NC) for comparison (Figures 3(e) and 3(f)). Parameter estimates for the Inhibitors,research,lifescience,medical simulations are listed in Table 1. Table 1 Parameter estimates for simulations in Figure 3. We first simulate the fast release of CF from TSL, triggered by mild hyperthermia (Figure 3(a)). Li et al. [24] designed and synthesized TSL such that its gel-to-liquid transition temperature resided at around 43°C. As a result, TSL was stable at 37°C and capable of retaining encapsulated molecules in the circulation. Once it reached the targeted site, TSL released encapsulated molecules rapidly due to and the gel-to-liquid transition induced by local hyperthermia. This process can be modulated by PEG addition. For instance, TSL with a high PEG density releases CF faster than TSL with a low PEG density. Our model successfully captures CF release from TSL with different PEG densities at 42°C. In particular, both ΔG and kS increase with PEG density, suggesting that PEGylation not only modifies the permeability of the lipid membrane but also decreases the ability of TSL to interact with hydrophilic molecules. This is consistent with the report [24] that PEG at a high density destabilizes the lipid membrane of TSL and changes the membrane modality for CF release.