Nanomedicine - Bionanoelectronics: Bioinquiring and Bioinspired Devices - page 128

The controlled delivery of drugs based on nanotechnologies is developed to increase
the efficiency of drug treatments and, at the same time, to reduce the adverse effects
that often accompany these treatments, as well as to enable new therapeutic methods
based on nanotechnologies. Over 20 therapeutic products based on nanotechnolo-
gies were approved for clinical use and much more are in clinical trial.
There are several generations of controlleddrugdeliverysystemsbasedon
nanotechnologies ( Riehemann et al. 2009 ). The first generation is a passive delivery
system, which localizes at the target, for example, a tumor. It is based on liposome,
termed as a nanovector, which is confined in the tumor by the enhanced permeation
and retention (EPR) effect or through the increased permeability of the tumor
neovasculature. Other nanovectors of the first generation are metallic nanoparticles
and albumin-paclitaxel nanoparticles, which are approved to be used in breast
cancer. All these nanovectors are functionalized on their surface with a stealth layer
such as polyethylene glycol (PEG) to avoid their early capture by the phagocytic
blood cells and hence to extend their circulation time.
The second nanovector generation has added functionalities, enabling controlled
release of various loads at the specific site of the disease or molecular recognition
of the target. The nanovectors are now able to target the tumors using antibodies
and other biomolecules used for tumor detection. The most known nanovectors
of this generation are liposomes and nanoparticles functionalized with antibodies.
Other functionalizations are studied and are based on aptamers, ligands, etc. This
second generation has the ability to remotely control the activation of nanovectors,
for example, to control iron oxide nanoparticles by switching a magnetic field, or to
use RF signals and ultrasounds as triggers.
The third generation of nanovectors is able to perform a multitude of tasks
such as the generation of multiple series of nanoparticles able to overcome various
biological barriers. This third generation will enable the connection of nanoparticles
and small interfering RNA (siRNA), which can suppress the action of genes that
cause cancer. Codelivery and coencapsulation are the key words for the nanovectors
of this last generation. Coencapsulation means the encapsulation of hydrophilic and
hydrophobic drugs, which are used to control the time of codelivery of drugs and
specific DNA sequences at the intracellular level ( Wang et al. 2006 ). Another exam-
ple is the incorporation in a single nanoparticle of multiple functions, such as simul-
taneous imaging and delivery of therapeutic biomolecules ( Bagalkot et al. 2007 ).
The MEMS/NEMS devices for drug delivery systems are also rapidly developing
( Hilt and Peppas 2005 ; Staples et al. 2006 ; Shi et al. 2010 ). At the end of Chap. 1 ,
we have explained some basic facts regarding the fabrication of MEMS devices
for micro/nanofluidics systems, while NEMS were explained in Chap. 2 in the
context of biosensing. In the case of drug delivery systems, the MEMS are used
for implantable microchips ( Ainslie and Desai 2008 ) that are able to codeliver
drugs in a prescribed manner using miniaturized pumps and reservoirs ( Tsai and
Sue 2007 ), micro- and nanoneedles for painless transdermal drug delivery, and patch
vaccination ( Prausnitz 2004 ). So, the MEMS/NEMS devices used for drug delivery
are of the third generation and are part of the large category of bioMEMS/NEMS.