Biomedical Engineering Reference
In-Depth Information
for 1 h and then increased to and retained at 180
C for the next 4 h to obtain
nanoparticles of Gd
2
O
3
.
7 Targeted Drug Delivery Using Nanoparticles
Targeted delivery of drug using nanoparticles is important for the following
reasons: (1) the unique pathophysiologic characteristics of tumor vessels enable
macromolecules, including nanoparticles, to selectively accumulate in tumor
tissues; (2) drug resistance has emerged as a major obstacle limiting the therapeutic
efficacy of chemotherapeutic agents, and among several mechanisms of drug
resistance, P-glycoprotein is the best known and most extensively investigated;
(3) intracellular and organelle-specific strategies are possible; (4) organ- or tissue-
specific drug delivery is possible; and (5) targeting.
7.1 Passive Targeting by Nanoparticles
7.1.1 Enhanced Permeability and Retention Effect
Nanoparticles that have the capability of escaping reticuloendothelial system cap-
ture can circulate for longer times in the bloodstream and, hence, have a greater
chance of reaching the targeted tumor tissues. The enhanced vasculature of a
growing tumor enables macromolecules, including nanoparticles, to selectively
accumulate in tumor tissues [
106
], since the existing vessels near the tumor mass
need a greater supply of oxygen and nutrients [
107
]. The resulting imbalance of
angiogenic regulators such as growth factors and matrix metalloproteinases makes
tumor vessels highly disorganized and dilated, with numerous pores showing
enlarged gap junctions between endothelial cells and with compromised lymphatic
drainage. These features are called the enhanced permeability and retention effect,
which constitutes an important mechanism by which macromolecules, including
nanoparticles, with a molecular weight above 50 kDa, can selectively accumulate in
the tumor interstitium.
7.2 Active Targeting by Nanoparticles
When the nanoparticle drug delivery vector is made more specific by the addition of
some target ligand or antibody, it is called active targeting [
108
]. One approach
suggested to overcome these limitations is the inclusion of a targeting ligand or
antibody in polymer-drug conjugates. Initially, direct conjugation of an antibody to
a drug was investigated. However, this approach was not successful during clinical
