Environmental Engineering Reference
In-Depth Information
One another innovative, one-step method of preparation of PMs consists of
lyophilization of the solution mixture of drug and polymer in a water-
tert
-butanol
system. Reconstitution of this freeze-dried cake of drug-polymer mixture with
injectable vehicle catalyzes spontaneous formation of PMs [
35
].
16.4 Polymeric Micelles in Drug Targeting
Beyond solubilizing hydrophobic drugs, block copolymer micelles can also target
their payload to specific tissues through either passive or active means. Drug-carrier
delivery systems employ biologically inert macromolecules to direct a drug to its
target site in the body. The major advantage of drug-carrier delivery systems is that
the distribution of drugs in the body depends on the physicochemical properties of
the carrier, not those of drugs. This implies that targeting can be manipulated by
choosing an appropriate carrier, or by alterations in the physicochemical properties
of the carrier. Targeting with drug-carrier systems can be divided into three types:
passive, active, and physical and these are described as follows:
(a) Passive Targeting. Passive targeting relies on the natural distribution pattern of
drug-carrier systems. For example, particles with a diameter of 5
mor
smaller are readily removed from the blood by macrophages of the RES
when administered systemically. This natural defense mechanism of the
RES thus provides an opportunity to target drugs to macrophages if they are
encapsulated in or conjugated with an appropriate carrier system. Passive
targeting also includes delivery of drug-carrier systems directly to a discrete
region in the body (different regions of GI tract, eye, rectum, vagina, respira-
tory tract, etc.). This offers the opportunity for the treatment of diseases that
require a persistent and sustained presentation of drugs at that site [
36
].
Initially it was thought that receptor-mediated targeting was the only way to
target the anticancer drugs to therapeutic sites; thus, many researchers have
developed engineered polymer micelle conjugates in which various ligands
have been attached to them. However, many recent studies have revealed that
polymer-conjugated drugs and nanoparticles show prolonged circulation in the
blood followed by passive accumulation in tumors even in the absence of
targeting ligands [
37
], demonstrating the existence of a passive retention
mechanism. Passive targeting of polymeric micelles to solid tumor can be
achieved through the enhanced permeability and retention (EPR) effect
[
38
]. In solid-tumor tissues, pathological, pharmacological, and biochemical
studies show that solid tumor generally possesses such pathophysiological
characteristics as hypervasculature, incomplete vasculature architecture,
secretion of vascular permeability factors stimulating extravasation, and
immature lymphatic capillaries [
39
]. Tumor vasculature has such characteris-
tics as a high proportion of proliferative endothelial cells, increased tortuosity,
pericyte deficiency, and aberrant basement membrane formation, resulting
ΚΌ
