Environmental Engineering Reference
In-Depth Information
Recently, the use of amphiphilic copolymer micelles has attracted much atten-
tion for solubilization of poorly soluble drugs. Suitable hydrophobic drugs which
may be incorporated into the copolymer micelles can be any bioactive agents
having limited solubility in aqueous environment. Without limiting the scope of
this carrier systems, suitable hydrophobic agents include anticancer drugs,
antipholgistic, anodynes, immunosupressants, hepatism remedies, homoine com-
positions, chemotherapeutics, metabolic pharmaceuticals, digestive disease reme-
dies, peripheral disease remedies, and circulatory disease remedies.
The reports on synthetic amphiphilic polymer micelles are well addressed in the
literature. A few excellent reviews have also been published [
17
-
22
] but they
focused mainly on the commercially available Pluronics
®
amphiphilic polymer
and other synthetic polymers decorated with hydrophilic poly (ethylene glycol)
segment. Natural polysaccharides are known to be nontoxic, biodegradable, easily
available, and amenable to various chemical modifications. Till date, the reports on
polysaccharide-based nanomicellar systems are scarce in the literature. This chapter
deals with the tailoring procedure for the natural polysaccharides, design of
polysaccharide-based nanomicellar reservoirs for delivering poorly water soluble
drugs to the target sites, its current state of the art, and future directions.
16.2 Surfactant and Polymer Micelles
Molecules or ions that are adsorbed at the interfaces are termed as surface active
agents or surfactants. Alternatively, it is called amphiphiles meaning that the
molecule or ion has a certain affinity for both polar and nonpolar solvents.
Depending on the number and nature of the polar and nonpolar groups present,
the amphiphiles may be predominantly hydrophilic, lipophilic, or reasonably well
balanced between these two extremes [
23
]. Surface active agents associate to form
colloidal aggregates termed micelles, which predominate in the system above a
certain concentration, called critical micelle concentration (CMC). Micelles have
the particle size normally within the 5-100-nm range. Micelles are formed when
amphiphiles are placed in water. They consist of an inner core of assembled
hydrophobic segments capable of solubilizing lipophilic substances and an outer
hydrophilic corona serving as a stabilizing interface between the hydrophobic core
and the external aqueous environment [
24
]. They physically entrap sparingly
soluble pharmaceuticals and deliver them to the desired site of action at concen-
trations that can exceed their intrinsic water solubility and thus increase their
bioavailability. In aqueous systems, nonpolar molecules are solubilized within the
micelle core, polar molecules will be adsorbed on the micelle surface, and sub-
stances with intermediate polarity will be distributed along surfactant molecules in
intermediate positions.
Kabanov et al. [
25
] suggested that they should be stable in vivo for a sufficiently
long time and should not provoke any biological reactions. They should release a
free drug upon contact with target tissues or cells; and, finally, the components of
