Micro and nanocarriers Micro and nanoscale technologies Oral drug delivery Tissue models Oral administration is a pillar of the pharmaceutical industry and yet it remains challenging to administer hydrophilic therapeutics by the oral route. Smart and controlled oral drug delivery could bypass the physiological barriers that limit the oral delivery of these therapeutics. Micro-and nanoscale technologies, with an unprecedented ability to create, control, and measure micro-or nanoenvironments, have found tremendous applications in biology and medicine. In particular, significant advances have been made in using these technologies for oral drug delivery. In this review, we briefly describe biological barriers to oral drug delivery and micro and nanoscale fabrication technologies. Micro and nanoscale drug carriers fabricated using these technologies, including bioadhesives, microparticles, micropatches, and nanoparticles, are described. Other applications of micro and nanoscale technologies are discussed, including fabrication of devices and tissue engineering models to precisely control or assess oral drug delivery in vivo and in vitro, respectively. Strategies to advance translation of micro and nanotechnologies into clinical trials for oral drug delivery are mentioned. Finally, challenges and future prospects on further integration of micro and nanoscale technologies with oral drug delivery systems are highlighted.

tissues, except at a very low concentration (0.044 ng/mg) in the liver, suggesting a very low risk 50 of systemic toxicity of locally delivered ATV. Additionally, the ex vivo data showed that ATV in 51 solution permeates through isolated human saphenous veins and thus is a good candidate for 52 perivascular delivery. 53Our data demonstrate that a local biphasic ATV release on the mice ligated carotid 54 efficiently prevents the development of IH without apparent toxicity. 55 56

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