b2815 Tissue Engineering and Nanotheranostics “9.61x6.69”
234 Tissue Engineering and Nanotheranostics
nanocarriers to form polymerbased prodrugs help circumvent prob
lems associated with solubility of anticancer drugs.^1 03–105 The polymer
based prodrugs can also enhance bioavailability of drugs, improve
chemodrug pharmacokinetics and pharmacological properties
through unique features of passively intratumoral accumulation.^104
Representative of synthetic polymeric nanomaterials are mainly N(2
hydroxypropyl) Methacrylamide (HPMA), poly(glutamic acid)
(PGA), poly(lacticcoglycolic acid) (PLGA), polyglycolides (PGCA),
which are mostly biodegradable and biocompatible with the human
body. HPMA, a water soluble, biocompatible and nonimmunogenic
polymer, provides a large number of pendent functional groups in
HPMA copolymers for drugs conjugation.106–108 Activating or releas
ing the drugs from the polymer backbone within a targeted region
can be carried out by manipulation of their bond, a degradable linker.
PGA is naturally synthesized in microbial species. It is a highly anionic
polymer which exhibits excellent biocompatibility and noncytotoxicity.
Researchers developed a thiolated PGA nanogel for the delivery of
doxorubicin (DOX) to treat MCF7 cancer cells, showing controlled
drug release behavior and higher toxicity as compared to free DOX.^109
PLGA, a Food and Drug Administration (FDA) approved biodegrad
able and biocompatible copolymer, is synthesized from the two poly
mers of poly(lactic acid) (PLA) and polyglycolicacid (PGA).^110 Many
anticancer drugs can be conjugated or directly loaded with PLGA,
and the conjugated or loaded drugs release from the complex, slowly
and over time.111,112 Natural polymers are commonly classified in to
three major categories: polysaccharides, polypeptides and polynucleo
tides. Among them, chitosan is widely applied as the drug delivery
systems.^1 13–115 For example, Nogueira et al. produced chitosan nano
particles loaded with anticancer agent of methotrexate for effective
therapy of cancer.^116 Dextran is a water soluble polymeric saccharide.
Dextranbased nanocarriers have been explored in in vitro, in vivo
and most recently.117,118 Pullulan is a natural polysaccharide with bio
degradable, nontoxic, nonmutagenic, and noncarcinogenic proper
ties. Due to the low immunogenicity and satisfactory solubility in
aqueous and several organic solvents, it has been widely used for
cancer drug delivery.119,120
