Factors Affecting the Acoustic In Vitro Release of Calcein from PEGylated Liposomes.

Typical methods used in cancer treatment, including chemotherapy, are debilitating because of the various adverse side effects experienced by cancer patients. The free drug injected into the patient at given doses affects both healthy and cancerous cells. Therefore, novel methods are being researched to ensure the selectivity of the treatment. The purpose of this study is to test the release of a model fluorescent drug, calcein, from echogenic stealth liposomes, triggered by lowfrequency pulsed ultrasound. Several experimental parameters related to the ultrasound (US) and the investigated liposomes were varied in order to examine their effect on the acoustic release. Upon analysis of experimental results, the study concluded that release can be maximized by optimizing the sonication frequency, power density, and US pulse duration. When a non-isothermal chamber is used to conduct the experiments, it is important to have longer 'Off' than 'On' US periods in order to avoid overheating the liposomes. Applying such pulsation pattern can also be utilized to achieve slower release rates, which safely meet the desired drug levels at the end of the session. Our study also concluded that optimizing the liposome concentration is vital to delivering desired drug doses. Additionally, the type of lipids used in the synthesis should be carefully selected to produce stable yet acoustically sensitive liposomes capable of releasing at desired rates.

Improving the Efficacy of Anticancer Drugs via Encapsulation and Acoustic Release.

Conventional chemotherapeutics lack the specificity and controllability, thus may poison healthy cells while attempting to kill cancerous ones. Newly developed nano-drug delivery systems have shown promise in delivering anti-tumor agents with enhanced stability, durability and overall performance; especially when used along with targeting and triggering techniques. This work traces back the history of chemotherapy, addressing the main challenges that have encouraged the medical researchers to seek a sanctuary in nanotechnological-based drug delivery systems that are grafted with appropriate targeting techniques and drug release mechanisms. A special focus will be directed to acoustically triggered liposomes encapsulating doxorubicin.

Use of Model Predictive Control and Artificial Neural Networks to Optimize the Ultrasonic Release of a Model Drug From Liposomes.

The use of echogenic liposomes to deliver chemotherapeutic agents for cancer treatment has gained wide recognition in the last 20 years. Cancerous cells can develop multiple drug resistance (MDR), in part, due to the drop in concentration of chemotherapeutic agents below the therapeutic levels inside the tumor. This suggests that MDR can be reduced by controlling the level of drug release in the diseased area. In this paper, a model predictive controller based on neural networks is proposed tomaintain a constant chemotherapeutic release at the cancer site. The proposed systemwas able to follow the set point by varying the U.S. intensity within preset constraints. The system simulated model is viable and it showed a high average fit when stimulated with variable input variations, indicating the robustness of the nonlinear model. By maintaining a constant release of the drug so that the concentration level is above a certain threshold, we hope to reduce cancer resistance towards chemotherapeutic agents.

Review on triggered liposomal drug delivery with a focus on ultrasound.

Chemotherapy is widely used for cancer treatment; however, it causes unwanted side effects in patients. To avoid these adverse effects, nanocarriers have been developed, which can be loaded with the chemotherapeutic agents, directed to the cancer site and, once there, are exposed to stimuli that will trigger the drug release. Liposomes can be chemically modified to increase their circulation time, their stability, and their sensitivity to specific stimulus. Additionally, ligands can be conjugated to their surface, allowing for their specific binding to receptors overexpressed on the surface of cancer cells and the subsequent internalization via endocytosis. Using a triggering mechanism, including temperature, ultrasound, enzymes or a change in pH, the release of the drug is controlled and induced inside the cells, hence avoiding drug release in systemic circulation, which in turn reduces the undesired side effects of conventional chemotherapy. Ultrasound has been widely studied as a drug release trigger from liposomes, due to its well-known physics and previous uses in medicine. This review focuses on liposome-based drug delivery systems, using different trigger mechanisms, with a focus on ultrasound. The physical mechanisms of ultrasound release are also investigated and the results of in vitro and in vivo studies are summarized.