9
degradation pathway of PEG, since enzymatic hydrolysis required contact between
PEG polymers and the active sites of enzymes. It is assumed that the mechanism of
decumulation of high Mw PEG after intravenous administration involves two
aspects: (i) hydrolytic depolymerization or chemical/enzymatic oxidation to degrade
high Mw PEG into small-sized fragments and (ii) renal excretion of low Mw PEG
(Carstens et al. 2008; Caliceti 2003).
On the other hand, amphiphilic polymers such as PEG-b-PCL have shown that
the PCL segments are easy to hydrolyze at 37 ° C and pH 5, while the PEG segments are not altered (Geng and Discher 2005). At the level of nanoparticles, e.g.
self-assembled micellar polymers of PEG (corona) and PCL (core) could have several erosion sites. If the corona formed by PEG is stable, erosion will occur at the
corona and core interface and then gradually extend to the core. In parallel, the
loaded drug will escape from the micelles (Fig. 2.1b). In case of degradation of PEG
decomposing enzymes, the micelles will undergo the bulk erosion throughout the
corona and the core.
2.3 PEG as a Hydrophilic Polymer
Hydrophilic polymers are a type of polymers that are easily dissolved or swollen by
water. This feature largely provided the biocompatibility and biodegradability of
these polymers. In pharmaceutical science, the conjugation of hydrophilic polymers
to hydrophobic drugs substantially improves their water solubility, thus increasing
the bioavailability of the desired drug (Kolate et al. 2014). In addition, the hydrophilicity of the nanoparticle delivery systems can be improved after introducing hydrophilic polymers on the surface of the nanoparticles (Soppimath et al. 2001). For
example, the core (hydrophobic)-shell (hydrophilic) structure nanoparticle interactions with the solvent and the biological liquid largely determine the drug circulating time within the body and, therefore, the final therapeutic efficacy (Joshy et al.
2017; Chen et al. 2018a).
PEG is a homogenous and linear polymer synthesized from ethylene oxide. PEG
is amphiphilic but highly water soluble. This noticeable hydrophilicity allows the
circulation and stability of PEG within the bloodstream (which mainly comprises
water) after intravenous administration. PEG is also biologically inert, which makes
it a ‘stealthy’ polymer that avoids recognition and adsorption of opsonin by plasma
proteins (Owens and Peppas 2006). By virtue of these desirable properties, PEG
becomes a representative example of synthetic hydrophilic polymers for the delivery of bioactive compounds, which can be tailor-designed for different applications
at the molecular level and nanoparticles. At the molecular level, PEG can be synthesized as a hydrophilic homopolymer of a conjugate, or as a hydrophilic subunit of
random or block copolymers. At the nanometric level, PEG can be manufactured in
a variety of physical forms, including crosslinked nanohydrogels, PEG block polymer micelles, physical mixtures or composites with other polymers and grafts on
the surfaces of other biomaterials.
2 Biodegradable and Functional Synthetic Polymers in Nanomedicine: Controlled…
degradation pathway of PEG, since enzymatic hydrolysis required contact between
PEG polymers and the active sites of enzymes. It is assumed that the mechanism of
decumulation of high Mw PEG after intravenous administration involves two
aspects: (i) hydrolytic depolymerization or chemical/enzymatic oxidation to degrade
high Mw PEG into small-sized fragments and (ii) renal excretion of low Mw PEG
(Carstens et al. 2008; Caliceti 2003).
On the other hand, amphiphilic polymers such as PEG-b-PCL have shown that
the PCL segments are easy to hydrolyze at 37 ° C and pH 5, while the PEG segments are not altered (Geng and Discher 2005). At the level of nanoparticles, e.g.
self-assembled micellar polymers of PEG (corona) and PCL (core) could have several erosion sites. If the corona formed by PEG is stable, erosion will occur at the
corona and core interface and then gradually extend to the core. In parallel, the
loaded drug will escape from the micelles (Fig. 2.1b). In case of degradation of PEG
decomposing enzymes, the micelles will undergo the bulk erosion throughout the
corona and the core.
2.3 PEG as a Hydrophilic Polymer
Hydrophilic polymers are a type of polymers that are easily dissolved or swollen by
water. This feature largely provided the biocompatibility and biodegradability of
these polymers. In pharmaceutical science, the conjugation of hydrophilic polymers
to hydrophobic drugs substantially improves their water solubility, thus increasing
the bioavailability of the desired drug (Kolate et al. 2014). In addition, the hydrophilicity of the nanoparticle delivery systems can be improved after introducing hydrophilic polymers on the surface of the nanoparticles (Soppimath et al. 2001). For
example, the core (hydrophobic)-shell (hydrophilic) structure nanoparticle interactions with the solvent and the biological liquid largely determine the drug circulating time within the body and, therefore, the final therapeutic efficacy (Joshy et al.
2017; Chen et al. 2018a).
PEG is a homogenous and linear polymer synthesized from ethylene oxide. PEG
is amphiphilic but highly water soluble. This noticeable hydrophilicity allows the
circulation and stability of PEG within the bloodstream (which mainly comprises
water) after intravenous administration. PEG is also biologically inert, which makes
it a ‘stealthy’ polymer that avoids recognition and adsorption of opsonin by plasma
proteins (Owens and Peppas 2006). By virtue of these desirable properties, PEG
becomes a representative example of synthetic hydrophilic polymers for the delivery of bioactive compounds, which can be tailor-designed for different applications
at the molecular level and nanoparticles. At the molecular level, PEG can be synthesized as a hydrophilic homopolymer of a conjugate, or as a hydrophilic subunit of
random or block copolymers. At the nanometric level, PEG can be manufactured in
a variety of physical forms, including crosslinked nanohydrogels, PEG block polymer micelles, physical mixtures or composites with other polymers and grafts on
the surfaces of other biomaterials.
2 Biodegradable and Functional Synthetic Polymers in Nanomedicine: Controlled…