Environmental Engineering Reference
In-Depth Information
Polymeric micelles can be used as efficient carriers for compounds, which alone
exhibit poor solubility, undesired pharmacokinetics, and low stability in a physio-
logical environment. The hydrophilic shell contributes greatly to the pharmaceuti-
cal behavior of polymeric formulations by maintaining the micelles in a dispersed
state, as well as by decreasing undesirable drug interactions with cells and proteins
through steric stabilization effects. There are significant differences between the
two types of assemblies from the physicochemical viewpoint. The polymer con-
centration at which the association first takes place, sometimes known as the critical
association concentration (CAC), is lower by several orders of magnitudes than
typical surfactant CMC values. They can increase drug bioavailability and reten-
tion, since the drug is well protected from possible inactivation under the effect of
their biological surroundings [
29
]. Polymeric micelles have been studied exten-
sively as delivery medium for injectable drug formulations of poorly soluble drugs
such as paclitaxel, indomethacin, amphotericin B, adriamycin, and dihydrotestos-
terone. Overall, they proved to be highly effective drug delivery vehicles.
Driving force for micelle formation is mainly based on the hydrophobic inter-
action, hydrogen bonding, metal complexation, and electrostatic interaction. In
order to modify these properties, functional groups are introduced to the core-
forming segments. Previous experiments have prompted reports that the polymeric
micelles from hydrophobic interactions remain stable in aqueous solutions for days.
The preparation of the polymeric micelle also involves the induction of strong
interactions between the core-forming blocks, such as electrostatic interaction, and
metal complexation. Basically, the reduction of free energy is the key factor for
preparing stable polymeric micelles. Therefore, it must be emphasized that entropy
change is not always the major driving force for micelle formation. When strong
cohesive forces such as hydrogen bonding and metal complexation are involved,
enthalpy change plays a more important role in the stabilization of polymeric
micelles. Indeed, the polymeric micelles prepared solely through the entropy-
driven mechanism dissociate easily under the diluted conditions, and therefore,
these micelles are not suitable for parenteral drug delivery.
The hydrophobic core of the polymeric micelles is expected to serve as the loading
space for various lipophilic drugs. By design, given the nanometer size of the
micelles, this space is limited. In order to exploit fully this loading space, one must
manipulate the many factors that control loading capacity and efficiency. In devising
a drug incorporation strategy, one must try to match as closely as possible the polarity
of the hydrophobic micelle core to the solubility characteristics of the drug.
The hydrophilic corona of polymeric micelles can be composed of various types
of polymers. PEG, the most commonly used shell-forming polymer, is one of the
few synthetic polymers approved by the Food and Drug Administration (FDA) for
internal use. Its biocompatibility and lack of toxicity have largely contributed to its
acceptance. When hydrated, PEG forms a dense brush of polymer chains stretching
out from the core of the micelle. Owing to its high aqueous solubility, high
mobility, and large exclusion volume [
30
], PEG imparts steric stability by mini-
mizing the interfacial free energy of the micellar core and by impeding hydrophobic
intermicellar attractions [
31
].
