the commonly adopted strategy is to modify the native material. For example,
starch can be easily degraded in presence of the enzyme amylase, which acts on
its hydroxyl groups. Hence, in order to obtain a slower release, the hydroxyl groups
of starch are modified with propyl, ethyl, or acetyl groups, thereby reducing both its
hydrophilicity and degradation rates [34, 35].
A study by Wilson et al. reports that chitosan nanoparticles, intended for the release
of the anti-Alzheimer drug tacrine, prepared through spontaneous emulsification are
stable at different temperatures (15–20
C, 3–5
C and 37
C), with no significant
change in physical appearance, particle size, drug content, or chemical interaction
between drug and polymer over a period of 3 months [102]. A study by Prego et al.
suggested high stability for ionically crosslinked polyethylene glycol (PEG)-grafted
chitosan as a gene carrier [103]. Surface modification of polylactic acid (PLA)
nanoparticles was done by using covalent attachment of PEG to PLA and physical
adsorption of water-soluble chitosan (WSC) to the particle surface. Two types of
WSC, cationic partially deacetylated chitin (PDC) and anionic N-carboxy propionyl
chitosan sodium (CPCTS), were investigated. The presence of WSC, whether alone or
with PEG, highly improved the surface hydrophilicity as well as suspension stability
of the nanoparticles [104]. Studies on nanoparticles of dextran esters for drug delivery
suggests that better colloidal stability can be attained when a dextran ester of low
degree of substitution is used in the aqueous phase, independent of the degree of
substitution of the dextran ester present in the core of the particle [27].
2.3.2 Stability of Proteins
Proteins as biomolecules are always liable to enzymatic degradation and digestion
as well as to changes in pH and temperature. On the other hand, the use of protein
nanocarriers to entrap drug molecules will help evade its uptake by the immune
system, prevent opsonization and its subsequent phagocytosis to a great extent,
improve circulation of the drug by renal and hepatic re-absorption, and much more.
Several techniques have been proposed in the literature to prevent the acid or
enzymatic degradation of protein nanocarriers [62, 93, 105, 106].
Physical integrity of the nanocarriers depends upon the preparation route and the
kind of crosslinker used. For gelatin, it is found that the use of gluteraldehyde (GA)
improves the stability of the nanocarriers. The encapsulated drug also alters the
stability of the carrier, as in the case of encapsulated doxorubicin improving the
stability of GA crosslinked gelatin nanocarriers. This is believed to be because of
the competition between the free amino groups of gelatin and doxorubicin during
the crosslinking process [7, 54]. However, the use of GA for controlling nanoparticle resiliency is a concern owing to its cytotoxicity and the fact that it may react
undesirably with the therapeutic agents entrapped within the nanoparticles [107].
To address this concern, several cationic polymers such as polyethyleneimine (PEI)
and poly-L-lysine (PLL), have been used for crosslinking purpose, thereby enhancing the stability of drug-loaded nanocarriers [108]. In a more recent study, the
thermal and mechanical properties of gelatin hydrogels were improved by
crosslinking them with biodegradable cellulose nanowhiskers [109].
Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems. . .
253
starch can be easily degraded in presence of the enzyme amylase, which acts on
its hydroxyl groups. Hence, in order to obtain a slower release, the hydroxyl groups
of starch are modified with propyl, ethyl, or acetyl groups, thereby reducing both its
hydrophilicity and degradation rates [34, 35].
A study by Wilson et al. reports that chitosan nanoparticles, intended for the release
of the anti-Alzheimer drug tacrine, prepared through spontaneous emulsification are
stable at different temperatures (15–20
C, 3–5
C and 37
C), with no significant
change in physical appearance, particle size, drug content, or chemical interaction
between drug and polymer over a period of 3 months [102]. A study by Prego et al.
suggested high stability for ionically crosslinked polyethylene glycol (PEG)-grafted
chitosan as a gene carrier [103]. Surface modification of polylactic acid (PLA)
nanoparticles was done by using covalent attachment of PEG to PLA and physical
adsorption of water-soluble chitosan (WSC) to the particle surface. Two types of
WSC, cationic partially deacetylated chitin (PDC) and anionic N-carboxy propionyl
chitosan sodium (CPCTS), were investigated. The presence of WSC, whether alone or
with PEG, highly improved the surface hydrophilicity as well as suspension stability
of the nanoparticles [104]. Studies on nanoparticles of dextran esters for drug delivery
suggests that better colloidal stability can be attained when a dextran ester of low
degree of substitution is used in the aqueous phase, independent of the degree of
substitution of the dextran ester present in the core of the particle [27].
2.3.2 Stability of Proteins
Proteins as biomolecules are always liable to enzymatic degradation and digestion
as well as to changes in pH and temperature. On the other hand, the use of protein
nanocarriers to entrap drug molecules will help evade its uptake by the immune
system, prevent opsonization and its subsequent phagocytosis to a great extent,
improve circulation of the drug by renal and hepatic re-absorption, and much more.
Several techniques have been proposed in the literature to prevent the acid or
enzymatic degradation of protein nanocarriers [62, 93, 105, 106].
Physical integrity of the nanocarriers depends upon the preparation route and the
kind of crosslinker used. For gelatin, it is found that the use of gluteraldehyde (GA)
improves the stability of the nanocarriers. The encapsulated drug also alters the
stability of the carrier, as in the case of encapsulated doxorubicin improving the
stability of GA crosslinked gelatin nanocarriers. This is believed to be because of
the competition between the free amino groups of gelatin and doxorubicin during
the crosslinking process [7, 54]. However, the use of GA for controlling nanoparticle resiliency is a concern owing to its cytotoxicity and the fact that it may react
undesirably with the therapeutic agents entrapped within the nanoparticles [107].
To address this concern, several cationic polymers such as polyethyleneimine (PEI)
and poly-L-lysine (PLL), have been used for crosslinking purpose, thereby enhancing the stability of drug-loaded nanocarriers [108]. In a more recent study, the
thermal and mechanical properties of gelatin hydrogels were improved by
crosslinking them with biodegradable cellulose nanowhiskers [109].
Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems. . .
253