Recent Progress in Polymer Therapeutics as Nanomedicines - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 82

or nucleophilic agents. PGA is water soluble, non-toxic, and
biodegradable. Cysteine proteases, particularly cathepsin B, play
key role in the lysosomal degradation of PGA. In addition, PGA has
a γ -carboxyl group in each repeating unit of L -glutamic acid that
off ers multivalent attachment to drugs. Those features make PGA
an attractive drug carrier, and indeed PGA-PTX (OPAXIO™, former
names XYOTAX and CT-2103) is the most progressed polymer-drug
conjugate in the pipeline for market approval [11, 12].
Several polysaccharides are being used as polymeric carriers [13,
14]. Among natural and semi-synthetic polysaccharides, hyaluronic
acid, chitosan, and dextran have been largely investigated for drug
bioconjugation [13]. Dextran is a natural polysaccharide containing
monomers of simple sugar glucose. This polyglucose biopolymer is
characterized by a-1,6 linkages, with hydroxylated cyclohexyl units
[14]. Dextran has been particularly popular owing to its clinical
approval for use as a plasma expander. Dextran is a water-soluble
biopolymer, but it can also dissolve in some organic solvents, such
as dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF)
formamide, ethylene glycol, and glycerol. Dextran is biocompatible
and biodegradable in blood and in the gastrointestinal (GI) tract.
However, it is not degraded in lysosomes. Dextran possesses multiple
primary and secondary hydroxyl groups that can be used for binding
drugs or proteins directly or via spacers [23].
Pullulan is another interesting natural, non-ionic, and linear
homopolysaccharide, formed by repeated units of maltotriose
condensed through α -1,6 linkage ( α -1,4-linked glucose molecules,
polymerized by α -1,6-linkages to the terminal glucose) [24]. Owing
to its excellent biological and physicochemical features, namely
biodegradability, low immunogenicity, and polyfunctionality together
with its fair solubility in aqueous and few organic solvents, pullulan
has become an attractive ingredient for many pharmaceutical
applications and chemical manipulations [25]. There are several
examples in the literature for the use of pullulan as a carrier, in
which the drug is conjugated to the primary hydroxyl groups via
ester bonds or through lysosomal-sensitive peptide spacers [26].

4.1.3 Non-Degradable Polymer Backbone

PEG has good water solubility, but it can also dissolve in many organic
solvents. This feature together with its biocompatibility has made