Nanomedicines for Systemic Delivery of RNAi Therapeutics - RNA Interference from Biology to Therapeutics - page 126

less toxic and have the potential to target specific cells. Studying gene expression in
a disease model by validating the specific role of the gene in vivo along with the
potential to induce therapeutic gene silencing opens new avenues for utilising RNAi
as a novel therapeutic modality. This review will present the recent progress in this
emerging field, focusing on the in vivo applications with special emphasis on the
strategies for RNAi delivery to leucocytes using various nanomedicines.

6.2 Nanomedicine

By definition, nanomedicine is the medical application of nanotechnology [ 26, 27 ] .
Nano-vehicles made from different materials with different size, geometry and
charge with at least one dimension within the range of 1-100 nm that are used for
delivery of imaging agents (for diagnostics) and/or for delivery of therapeutic enti-
ties are termed nanomedicine [ 26, 27 ] or nano-drug. In addition, a new class of
vehicles that can deliver both diagnostics agents and therapeutic agents and can
report in real-time the location of a diseased cell/tissue is termed theranostics (diag-
nosis and therapy), and it is considered as the next-generation approach of current
nano-scale delivery platforms. The reader is referred to recent excellent reviews on
nanomedicines with various applications, which are beyond the scope of this chap-
ter [ 28- 31 ]. In this chapter, the term “nanomedicine” will be used for any delivery
system at the nanoscale.

6.3 Translation of RNAi into Clinical Practice

Despite the large diversity of available methods for in vitro siRNA delivery briefly
described above, there are additional hurdles to translate these methods into a
clinical therapeutic. As detailed below, the biggest hurdle facing the translation of
RNAi therapeutic potential into the clinic is their delivery.

6.3.1 In Vivo Delivery of siRNAs

Most common routes of administration of siRNAs include the preferred non-invasive
per-oral, topical (skin), transmucosal (nasal, pulmonary, buccal, sublingual, vaginal,
ocular and rectal) as well as systemic (intravenous) administration.
Local delivery of siRNAs has been demonstrated in various animal models [ 22,
32- 34 ] and is employed in several ongoing clinical trials. Based on local injections
of naked or cationic lipid/polymer-formulated siRNAs, this method of treatment