12 Polysaccharides
Polysaccharide nanoparticles have been extensively used in biomedical applications
due to their biocompatibility, biodegradability, high abundance, and low toxicity
[125, 126]. The wide range of biological activities of polysaccharides arises from
the great diversities of their chemical composition. For instance, the glycan-directed
binding abilities of polysaccharides to different body tissues can be used in targeted
drug delivery applications. In addition, polysaccharides can be readily functionalized
through their intrinsic multiple hydroxyl groups. The most commonly used
polysaccharides are chitosan, alginate, hyaluronan, dextran, heparin, chondroitin
sulfate, amylose, pullulan, arabinogalactan, and cyclodextrins. NPs have been
synthesized from polysaccharides using various methods. Typical methodologies
include: (a) crosslinking between different polymers (one example is discussed in
the section on nanogels); (b) formation of interpolymer complexes through electrostatic interactions between oppositely charged polysaccharides; (c) self-assembly of
amphiphilic hydrophobic groups grafted onto polysaccharides; and (d) from
polymer–drug conjugates (one example is discussed in the next section). The inherent
ionic charges associated with polysaccharides have been successfully used for encapsulation and delivery of oppositely charged drugs and biomacromolecules.
Polysaccharides have also been coated to the surface of nanoparticles to achieve
increased stability, long-term circulation, and targeting abilities for drug delivery
applications.
13 Miscellaneous Examples
Lee and coworkers designed a pH-sensitive chitosan-based drug conjugate 122 for
photodynamic therapy (Fig. 23) [127]. Chitosan polymers were functionalized with
3-diethylaminopropyl isothiocyanate (DEAP), chlorine e6 (Ce6, used as a
photosensitizing model drug) and a PEG block. The drug conjugate was selfassembled in aqueous solution such that the hydrophobic DEAP and Ce6 were
located at the hydrophobic core, while the hydrophilic PEG and CSG polymers
were exposed at the hydrophilic surface of the self-assemblies. The importance of
the drug conjugate 122 resides in its conformational change under pH variation
from 7.4 (normal tissue pH) to 6.8 (pH in the tumor microenvironment). With a
change in pH from 7.6 to 6.8, the coiled assembly structure (self-quenched state of
Ce6, not suitable for singlet-oxygen production) undergoes a conformational
change to form uncoiled extended random molecules (de-quenched state of Ce6
suitable for singlet-oxygen formation) (Fig. 23). The protonation of the DEAP
block within the conjugate 122 at pH 6.8 was responsible for the conformational
change. Fluorescence studies demonstrated that the “singlet-oxygen productivity”
of the drug conjugate 122 at pH 6.8 was similar to that of free Ce6, whereas that at
pH 7.4 was found to be low, hence confirming the uncoiled structure of 122 at pH
6.8 with the de-quenched state of Ce6 suitable for singlet-oxygen formation.
332
N. Kottari et al.
Polysaccharide nanoparticles have been extensively used in biomedical applications
due to their biocompatibility, biodegradability, high abundance, and low toxicity
[125, 126]. The wide range of biological activities of polysaccharides arises from
the great diversities of their chemical composition. For instance, the glycan-directed
binding abilities of polysaccharides to different body tissues can be used in targeted
drug delivery applications. In addition, polysaccharides can be readily functionalized
through their intrinsic multiple hydroxyl groups. The most commonly used
polysaccharides are chitosan, alginate, hyaluronan, dextran, heparin, chondroitin
sulfate, amylose, pullulan, arabinogalactan, and cyclodextrins. NPs have been
synthesized from polysaccharides using various methods. Typical methodologies
include: (a) crosslinking between different polymers (one example is discussed in
the section on nanogels); (b) formation of interpolymer complexes through electrostatic interactions between oppositely charged polysaccharides; (c) self-assembly of
amphiphilic hydrophobic groups grafted onto polysaccharides; and (d) from
polymer–drug conjugates (one example is discussed in the next section). The inherent
ionic charges associated with polysaccharides have been successfully used for encapsulation and delivery of oppositely charged drugs and biomacromolecules.
Polysaccharides have also been coated to the surface of nanoparticles to achieve
increased stability, long-term circulation, and targeting abilities for drug delivery
applications.
13 Miscellaneous Examples
Lee and coworkers designed a pH-sensitive chitosan-based drug conjugate 122 for
photodynamic therapy (Fig. 23) [127]. Chitosan polymers were functionalized with
3-diethylaminopropyl isothiocyanate (DEAP), chlorine e6 (Ce6, used as a
photosensitizing model drug) and a PEG block. The drug conjugate was selfassembled in aqueous solution such that the hydrophobic DEAP and Ce6 were
located at the hydrophobic core, while the hydrophilic PEG and CSG polymers
were exposed at the hydrophilic surface of the self-assemblies. The importance of
the drug conjugate 122 resides in its conformational change under pH variation
from 7.4 (normal tissue pH) to 6.8 (pH in the tumor microenvironment). With a
change in pH from 7.6 to 6.8, the coiled assembly structure (self-quenched state of
Ce6, not suitable for singlet-oxygen production) undergoes a conformational
change to form uncoiled extended random molecules (de-quenched state of Ce6
suitable for singlet-oxygen formation) (Fig. 23). The protonation of the DEAP
block within the conjugate 122 at pH 6.8 was responsible for the conformational
change. Fluorescence studies demonstrated that the “singlet-oxygen productivity”
of the drug conjugate 122 at pH 6.8 was similar to that of free Ce6, whereas that at
pH 7.4 was found to be low, hence confirming the uncoiled structure of 122 at pH
6.8 with the de-quenched state of Ce6 suitable for singlet-oxygen formation.
332
N. Kottari et al.