Drug Delivery Systems Based on Polymeric Micelles and Ultrasound: A Review

Background: Anti-neoplastic drugs used for cancer treatment often produce damage to healthy cells, leading to severe side effects in patients undergoing chemotherapy. The encapsulation of these agents in nanoparticles reduces the adverse side effects of conventional chemotherapy on healthy tissues. Such nanoparticles, considered as drug delivery vehicles, are diverse and include micelles, liposomes, dendrimers, nanocapsules, nanospheres and others. Polymeric micelles have been widely researched as nanocarriers for hydrophobic drugs. They can be designed to have increased stability and blood circulation time, as well as binding specificity to certain receptors overexpressed on the surface of cancer cells. Once these drug-encapsulating nanoparticles reach the tumor site, an external stimulus, such as ultrasound, can be used to spatially and temporally trigger drug release. Methods: This review paper focuses on the recent advances of cancer drug delivery systems employing polymeric micelles and ultrasound. An extensive literature review was performed mainly using PubMed. The introduction explains how nanocarriers are related to chemotherapy and the several modalities of use for this application. Afterwards, the review focuses on polymeric micelles used for drug delivery, their advantages and disadvantages. Subsequently, the physics of ultrasound is briefly reviewed, as well as the way it interacts with polymeric micelles to trigger the delivery of the drug transported by these nanocarriers. The following section focuses on targeting, discussing the several ways by which the nanoparticles can be directed to the target cells, and there deliver their cargo. Finally, a selection of relevant in vitro and in vivo studies, as well as clinical trials, is presented and discussed. Conclusion: Although there are still several research studies to be performed before the combination of micelles and ultrasound can enter clinical trials, the future of controlled delivery using this drug delivery system is promising as a way to reduce the mortality and morbidity of cancer and the noxious side effects of conventional chemotherapy.