No abstract

One application of nanotechnology in medicine that is presently being developed involves a drug delivery system (DDS) employing nanoparticles to deliver drugs to diseased sites in the body avoiding damage of healthy tissue. Recently, the mild hyperthermia-triggered drug delivery combined with anticancer agent-loaded thermosensitive liposomes was widely investigated. In this study, thermosensitive liposomes (TSLs), composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG), cholesterol, and a fatty acid conjugated elastin-like polypeptide (ELP), were developed and optimized for triggered drug release, controlled by external heat stimuli. We introduced modified ELP, tunable for various biomedical purposes, to our thermosensitive liposome (e-TSL) to convey a high thermoresponsive property. We modulated thermosensitivity and stability by varying the ratios of e-TSL components, such as phospholipid, ELP, and cholesterol. Experimental data obtained in this study corresponded to results from a simulation study that demonstrated, through the calculation of the lateral diffusion coefficient, increased permeation of the lipid bilayer with higher ELP concentrations, and decreased permeation in the presence of cholesterol. Finally, we identified effective drug accumulation in tumor tissues and antitumor efficacy with our optimized e-TSL, while adjusting lag-times for systemic accumulation.

Liposomal drug delivery products have been already commercialized in tumor therapeutics, which can realize passive tumor targeting via enhanced permeability and retention (EPR) effect resulting from the leaky tumor vasculature. To control drug release out of the liposomes, thermo-sensitive liposomes (TSLs) have been developed so that an abrupt exposure of highly concentrated drugs to tumor tissues was enabled by locally treated thermal stimuli. As interests upon TSL have increased along with ongoing clinical trials, some types of TSLs with different physical properties in pharmacokinetics and the mechanism of drug release have been formulated. However, there are few protocols established with a desirable heat source to maximize the efficacy of different TSLs as treating tumors. In this study, we examined different protocols for the most effective application of different TSLs to tumor therapy. First, we examined if enhancing the accumulation of TSLs within tumor tissues prior to bursting drugs out of TSLs could lead to increasing anti-tumor efficacy. Second, we compared the efficiency of two different heat sources on the use of TSL, a warm water bath (42 o C) and high intensity focused ultrasound (HIFU). Our study suggests that the specified protocol be setup for TSLs with different physical properties to optimally function in tumor therapies.