2.1.1 Drug Loading Properties of Carbohydrates
Chitosan, a versatile cationic polysaccharide of natural origin, is extensively
explored for loading various kinds of drug molecules, genes, etc. For instance,
cisplatin, a hydrophilic drug, was loaded into chitosan matrix during the preparation of nanoparticles with an encapsulation efficiency of ~99% [20]. It was
observed that neither the amount of crosslinker nor the drug had any effect on
drug loading. The major parameter that influenced drug loading was the polymer
concentration, which was directly proportional to the percentage drug loading.
Likewise, other hydrophobic drugs and drugs that precipitate in acidic pH (such as
diclofenac sodium) were also loaded into chitosan via the incubation method. In
this case, the influencing parameter was the crosslinker concentration, since the
drug was loaded into the polymer during its swelling process. Because higher
crosslinking decreased the swelling, the loading efficiency was proportionately
reduced [21]. Chitosan as well as derivatives like O-carboxymethylchitosan, N,Ocarboxymethylchitosan, chitin, etc. in nanoparticulate form have also demonstrated
reasonable success in the encapsulation and delivery of various types of anticancer
drugs (curcumin, 5-flurouracil, and polyoxometalates) and antibiotics (tetracyline,
etc.) when formulated by ionotropic gelation with the use of sodium
tripolyphosphate (TPP) or calcium chloride as the crosslinker [22–24]. However,
in certain cases, the drug itself can act as a crosslinker for the polymer, resulting in
its high entrapment. For instance, in the case of polyoxometalate (POM)-chitosan
nanocomplex, where the anionic POM is crosslinked with cationic chitosan, a good
entrapment of ~65% resulted in comparison to ~35% with the use of the routine
crosslinker, TPP [25].
Similarly, dextran, a bacterial polysaccharide with neutral charge that is well
known for its degradability by dextranase, biocompatibility, and nontoxicity, has
been explored for drug delivery wherein active molecules are either incorporated or
incubated in the nanoparticles [14, 26, 27]. Furthermore, for improved bioavailability of hydrophobic moieties, an alternative approach of covalent or non-covalent
attachment of drug molecules along dextran chains and use of dextran derivatives
like carboxymethyl dextran [28] or conjugates of dextran with other carbohydrates
like chitosan [29] is found to be useful.
Hyaluronan (HA) is a biodegradable, biocompatible linear polysaccharide that is
abundantly present in the extracellular matrix, connective tissues, and organs of all
higher animals and is metabolized through enzymatic hydrolysis [30, 31]. However,
HA being a carbohydrate with poor biomechanical properties, is less explored for
drug delivery in its native form. To facilitate this, various chemical modifications
through carboxyl and hydroxyl groups are performed to obtain mechanically and
chemically robust HA derivatives that retain the biocompatibility and biodegradability, but differ considerably in their physicochemical properties. Studies
performed with hyaluronic acid, the esterified derivative of HA, demonstrate better
encapsulation of hydrophilic than hydrophobic drugs due to the partial diffusion of
drug molecules from the aqueous phase to the external continuous oil phase during
246
D. Narayanan et al.
Chitosan, a versatile cationic polysaccharide of natural origin, is extensively
explored for loading various kinds of drug molecules, genes, etc. For instance,
cisplatin, a hydrophilic drug, was loaded into chitosan matrix during the preparation of nanoparticles with an encapsulation efficiency of ~99% [20]. It was
observed that neither the amount of crosslinker nor the drug had any effect on
drug loading. The major parameter that influenced drug loading was the polymer
concentration, which was directly proportional to the percentage drug loading.
Likewise, other hydrophobic drugs and drugs that precipitate in acidic pH (such as
diclofenac sodium) were also loaded into chitosan via the incubation method. In
this case, the influencing parameter was the crosslinker concentration, since the
drug was loaded into the polymer during its swelling process. Because higher
crosslinking decreased the swelling, the loading efficiency was proportionately
reduced [21]. Chitosan as well as derivatives like O-carboxymethylchitosan, N,Ocarboxymethylchitosan, chitin, etc. in nanoparticulate form have also demonstrated
reasonable success in the encapsulation and delivery of various types of anticancer
drugs (curcumin, 5-flurouracil, and polyoxometalates) and antibiotics (tetracyline,
etc.) when formulated by ionotropic gelation with the use of sodium
tripolyphosphate (TPP) or calcium chloride as the crosslinker [22–24]. However,
in certain cases, the drug itself can act as a crosslinker for the polymer, resulting in
its high entrapment. For instance, in the case of polyoxometalate (POM)-chitosan
nanocomplex, where the anionic POM is crosslinked with cationic chitosan, a good
entrapment of ~65% resulted in comparison to ~35% with the use of the routine
crosslinker, TPP [25].
Similarly, dextran, a bacterial polysaccharide with neutral charge that is well
known for its degradability by dextranase, biocompatibility, and nontoxicity, has
been explored for drug delivery wherein active molecules are either incorporated or
incubated in the nanoparticles [14, 26, 27]. Furthermore, for improved bioavailability of hydrophobic moieties, an alternative approach of covalent or non-covalent
attachment of drug molecules along dextran chains and use of dextran derivatives
like carboxymethyl dextran [28] or conjugates of dextran with other carbohydrates
like chitosan [29] is found to be useful.
Hyaluronan (HA) is a biodegradable, biocompatible linear polysaccharide that is
abundantly present in the extracellular matrix, connective tissues, and organs of all
higher animals and is metabolized through enzymatic hydrolysis [30, 31]. However,
HA being a carbohydrate with poor biomechanical properties, is less explored for
drug delivery in its native form. To facilitate this, various chemical modifications
through carboxyl and hydroxyl groups are performed to obtain mechanically and
chemically robust HA derivatives that retain the biocompatibility and biodegradability, but differ considerably in their physicochemical properties. Studies
performed with hyaluronic acid, the esterified derivative of HA, demonstrate better
encapsulation of hydrophilic than hydrophobic drugs due to the partial diffusion of
drug molecules from the aqueous phase to the external continuous oil phase during
246
D. Narayanan et al.