Potential and problems in ultrasound-responsive drug delivery systems

Abstract

Abstract:Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington's disease, thrombolysis, and disruption of the blood-brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future.

A Review of Low-Intensity Ultrasound for Cancer Therapy

“…The concept of a theranostic microbubble which can combine a chemotherapeutic role with ultrasound imaging is receiving increased attention (Peyman et al 2013; Zhao et al 2013). The bubble is loaded with a chemotherapeutic agent that is released in a tumor under the action of low-intensity ultrasound; the bubbles may also act as a contrast agent and used for contrast enhanced power Doppler ultrasound imaging of the tumor vasculature.…”

“…During tumor insonation, cavitation ruptures the bubble so releasing the drug and delivering it into the tumor - it may impart a "ballistic effect" to drive the drug through the wall of the tumor capillary (Liu et al 2006[a]). Also sonication can oscillate the microbubbles resulting in an increase in the permeability of the contiguous cell membranes including those of the endothelial cells lining tumor capillaries and further enhance the entry of a locally released chemotherapeutic agent into a cancer cell (Feril and Tachibana 2012; Stride and Coussios 2010; Zhao et al 2013). Following insonation (1.5 MHz, pulsed, 1.0 W.cm −2 ), of a rat glioma cell culture, fibered confocal fluourescence microscopy demonstrated in real time the intracellular delivery of an impermeable green dye from the microbubble into the cancer cell (Derieppe et al 2013).…”

“…magnetic resonance (MR) imaging in addition to ultrasound imaging; the topic has recently been briefly reviewed (Owen et al 2012; Zhao et al 2013). Niu et al (2013) developed such a multifunctional theranostic agent in which pelvic limb lymph node metastases from an implanted squamous cell carcinoma in rabbits were imaged by both MR and ultrasound.…”

Design strategies for physical-stimuli-responsive programmable nanotherapeutics

“…(2017) [102] showed that ultrasound could even disrupt solid inelastic polymeric nanoparticles made by 3,4-dihydro-2H-pyran- co -2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl methacrylate- co -2-(dimethylamino) ethyl methacrylate copolymer. Apart from its vesicular nanocarrier destabilizing effect, the mechanical cavitation applied to the tissue by ultrasound could also enhance nanoparticle extravasation across blood capillaries and penetration across cell membranes [100,107]. …”

“…Furthermore, ultrasound-responsive nanomaterials can also be designed by incorporating drugs into various ultrasound contrast agents [107,108]. The ultrasound-induced hyperthermia can also be used to generate gas bubbles for vascular occlusion and ablation of cancer cells [109].…”