emulsification [32]. Also, the fact that HA can bind to specific cellular receptors
such as CD44 makes it promising for targeting antitumor drugs towards various
tumors [33].
Starch is a comparatively less explored polymer for drug delivery due to its
extreme hydrophilicity. Hence, hydrophobically modified starch derivatives are
attracting interest in pharmaceutical research, due to their better entrapment and
sustained release. Studies with propyl-, acetyl-, and hydroxyethyl-modified forms
of starch have enabled enhanced entrapment through crosslinking and emulsion
routes of preparation [34, 35]. Drug loading can also be improved by crosslinking
anionic starch with cationic polymers such as chitosan, dextran, etc. [36, 37]. The
parameters that crucially influence drug loading include the polymer-to-crosslinker
ratio, reaction time, and temperature [38, 39].
Alginate, a linear, unbranched polysaccharide has also earned considerable
attention in biomedical research owing to its biocompatibility and abundance.
However, this carbohydrate (as in the case of starch) is afflicted by its hydrophilicity. Nonetheless, its ability to form a gel in the presence of cations makes it a
potential candidate for drug delivery. The mass relation between calcium (popularly used as crosslinker for alginate) and alginate is the major parameter in
determining the encapsulation efficiency [40, 41].
2.1.2 Drug Loading Properties of Proteins
Owing to the differing molecular weights, chemical complexity, and hydrophilicity,
each protein exhibits a varying degree of drug loading [4, 42, 43]. Albumin is a
nontoxic, biocompatible, and easily metabolizable protein that is widely
investigated as a drug carrier, owing to its abundance. It is commercially derived
from three major sources, viz., egg white (ovalbumin), bovine serum (BSA), and
human serum (HSA). Albumin is an interesting drug delivery agent mainly because
of its high affinity to a large number of drugs [42, 44]. It contains a large number of
charged amino acids and multiple binding sites, making it ideal for binding both
positively and negatively charged molecules. The traditional drug encapsulation
strategies for albumin-based drug carriers is to either entrap the drug “inside” the
nanocarrier or to attach the drug “onto” the surface of the proteins [7]. Abraxane is a
paclitaxel–albumin conjugated chemodrug, prepared by nab (nanoparticle albuminbound) technology, for treating advanced breast cancer [45]. Nab technology – the
technique of conjugating drug molecules onto a protein surface [46, 47] – also
serves as the platform for entrapping other anticancer drugs like docetaxel,
rapamycine, topoisomerase inhibitors, and other taxanes onto albumin
nanoparticles [44, 48]. In a recent study, the antiviral drug Ganciclovir was
entrapped in albumin nanocarriers at an efficiency that ranged from 40 to 65%
depending on the method of its preparation [49]. A high entrapment efficiency of
~80% was obtained upon loading sodium ferulate in albumin nanoparticles
subsequent to crosslinking the protein molecules with glutaraldehyde [50]. Likewise, entrapment and loading efficiencies of ~93% and 27%, respectively, were
Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems. . .
247
such as CD44 makes it promising for targeting antitumor drugs towards various
tumors [33].
Starch is a comparatively less explored polymer for drug delivery due to its
extreme hydrophilicity. Hence, hydrophobically modified starch derivatives are
attracting interest in pharmaceutical research, due to their better entrapment and
sustained release. Studies with propyl-, acetyl-, and hydroxyethyl-modified forms
of starch have enabled enhanced entrapment through crosslinking and emulsion
routes of preparation [34, 35]. Drug loading can also be improved by crosslinking
anionic starch with cationic polymers such as chitosan, dextran, etc. [36, 37]. The
parameters that crucially influence drug loading include the polymer-to-crosslinker
ratio, reaction time, and temperature [38, 39].
Alginate, a linear, unbranched polysaccharide has also earned considerable
attention in biomedical research owing to its biocompatibility and abundance.
However, this carbohydrate (as in the case of starch) is afflicted by its hydrophilicity. Nonetheless, its ability to form a gel in the presence of cations makes it a
potential candidate for drug delivery. The mass relation between calcium (popularly used as crosslinker for alginate) and alginate is the major parameter in
determining the encapsulation efficiency [40, 41].
2.1.2 Drug Loading Properties of Proteins
Owing to the differing molecular weights, chemical complexity, and hydrophilicity,
each protein exhibits a varying degree of drug loading [4, 42, 43]. Albumin is a
nontoxic, biocompatible, and easily metabolizable protein that is widely
investigated as a drug carrier, owing to its abundance. It is commercially derived
from three major sources, viz., egg white (ovalbumin), bovine serum (BSA), and
human serum (HSA). Albumin is an interesting drug delivery agent mainly because
of its high affinity to a large number of drugs [42, 44]. It contains a large number of
charged amino acids and multiple binding sites, making it ideal for binding both
positively and negatively charged molecules. The traditional drug encapsulation
strategies for albumin-based drug carriers is to either entrap the drug “inside” the
nanocarrier or to attach the drug “onto” the surface of the proteins [7]. Abraxane is a
paclitaxel–albumin conjugated chemodrug, prepared by nab (nanoparticle albuminbound) technology, for treating advanced breast cancer [45]. Nab technology – the
technique of conjugating drug molecules onto a protein surface [46, 47] – also
serves as the platform for entrapping other anticancer drugs like docetaxel,
rapamycine, topoisomerase inhibitors, and other taxanes onto albumin
nanoparticles [44, 48]. In a recent study, the antiviral drug Ganciclovir was
entrapped in albumin nanocarriers at an efficiency that ranged from 40 to 65%
depending on the method of its preparation [49]. A high entrapment efficiency of
~80% was obtained upon loading sodium ferulate in albumin nanoparticles
subsequent to crosslinking the protein molecules with glutaraldehyde [50]. Likewise, entrapment and loading efficiencies of ~93% and 27%, respectively, were
Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems. . .
247