Triggered Drug Release and Enhanced Drug Transport from Ultrasound-Responsive Nanoparticles
Conventional systemic drug therapy across all drug classes does not adequately provide safe and efficacious treatment for a broad range of fatal diseases. To address this challenge, there have been major advances in stimulus-responsive technologies for ac
- PDF / 725,917 Bytes
- 21 Pages / 439.37 x 666.14 pts Page_size
- 11 Downloads / 156 Views
1
Introduction
There have been major advances in the ability to discover and develop novel drugs across nearly all diseases and drug classes [1–3]. However, for most fatal diseases, such as cancers, cardiovascular diseases, and neurological disorders, the therapeutic agents typically used are effective in treating the diseased tissue, but are either excessively toxic [4–7] or poorly distributed within the diseased tissue [8–11]. These limitations in drug delivery have impacted all routes of transport, such as: oral, nasal, aerosol, transdermal, and systemic. Each of the aforementioned drug delivery routes has their own associated set of challenges and opportunities. However, the scope of this chapter is focused on systemic drug delivery because it is one of the most widely used means of delivering a drug. Efficacious yet highly toxic and nonspecific drugs often have limited bioavailability and distribution within diseased tissue [12]. These physiological challenges are not unique to specific diseases, but are present across cancers, cardiovascular lesions and occlusions, and the brain [13], and are therefore drug-class-agnostic. The need to overcome these challenges has resulted in a substantial increase in research devoted to techniques that promote site-targeted delivery and enhanced distribution of therapeutics. Many research groups have approached this need through a variety of “passive” and “active” drug delivery techniques. In this chapter, we focus on active processes that promote drug delivery in response to an ultrasound field.
J.J. Kwan • C.C. Coussios (*) Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford OX3 7DQ, UK e-mail: [email protected] © Springer International Publishing Switzerland 2017 J.W.M. Bulte, M.M.J. Modo (eds.), Design and Applications of Nanoparticles in Biomedical Imaging, DOI 10.1007/978-3-319-42169-8_13
277
278
2 2.1
J.J. Kwan and C.C. Coussios
Applications of Drug Therapies Cancer
Solid tumors represent a highly challenging environment for drug delivery, because of the chaotic vasculature, enhanced intratumoral pressure, dense extracellular matrix, and increased distance between a cancerous cell and the nearest blood vessel [14]. Tumors also present an unusual drug delivery opportunity by virtue of the leaky endothelial gaps that are typically present: this implies preferential accumulation or passage of therapeutics in the range 100–300 nm. Active delivery mechanisms typically have three roles to play in this context: enable increased extravasation of the therapeutic from the blood stream into the tumor, permit triggered release of the therapeutic at the tumor site only, and mediate improved transport and distribution of the therapeutic throughout the tumor mass. Conventional chemotherapeutics include small molecular drugs, such as taxanes (e.g., paclitaxel [15]), anthracyclines (e.g., doxorubicin [16, 17]), and cytosines (e.g., arabinoside [18, 19]), which typically circulate well and have considerable diffusivi
Data Loading...
