Polysaccharide-Based Anticancer Prodrugs

Abstract

So far, polysaccharides have been widely used in pharmaceutical technology as first choice excipients for production of traditional formulations. Nevertheless, in the recent years these natural and semisynthetic macromolecules have been addressed for new challenging applications as functional materials for innovative formulations. Their peculiar physicochemical and biological properties have been exploited to develop macromolecular prodrugs which can exhibit favorable biopharmaceutical properties and enforce the therapeutic performance of the parent drugs. These polymers display, in fact, high biocompatibility and biodegradability, multiple insertion points, and biological properties that can be advantageously exploited in drug delivery. In particular, the multifunctional structures of these polymers are anchoring points for conjugation of several anticancer drugs, which usually suffer from poor physicochemical, biopharmaceutical, and therapeutic properties that limit their therapeutic performance and proper use in anticancer treatment. Polysaccharide-based anticancer prodrugs can be designed to endow derivatives with new bioresponse, targeting, or environmental triggering properties or to combine molecules with synergistic therapeutic effect. Over the years, a variety of synthetic protocols have been set up to conjugate anticancer drugs to the polysaccharide backbone via specific linkages or through spacers which convey to the conjugates selective drug-delivery properties. Furthermore, the intrinsic antitumor activity and cell-targeting properties of few polysaccharides represent an additional value to the final therapeutic systems. Anticancer drugs with different pharmacodynamic, pharmacokinetic, and physicochemical properties have been successfully conjugated to various natural and semisynthetic polysaccharides highlighting the interesting perspectives for exploitation of new promising anticancer polymer therapeutics.

Fucoidan and Cancer: A Multifunctional Molecule with Anti-Tumor Potential

“…Polysaccharides include a large family of diverse biopolymers. They are constituted by monosaccharide residues linked together by O -glycosidic bonds that are found in natural and semi-synthetic structures [ 8 ]. Due to structural diversity, polysaccharides display the highest biological properties among macromolecules.…”

“…Many natural polysaccharides obtained from natural sources such as plants and algae have anti-cancer properties. The multifunctional structure of natural polysaccharides also allows them to be used in conjugation with anti-cancer agents that lack physiochemical and biopharmaceutical properties [ 8 , 9 ].…”

Hyaluronated mesoporous silica nanoparticles for active targeting: influence of conjugation method and hyaluronic acid molecular weight on the nanovector properties

“…Surface modification of nanocarriers through macromolecules is particularly relevant in the field of cancer treatment [32], where the conjugation of cytotoxic drugs with macromolecules is designed to improve their pharmacokinetic profile, prolonging the distribution and elimination phases [33]. The most employed are N-(2-hydroxypropyl) methacrylamide (HPMA), polyglutamate, human serum albumin, dextrans, heparin, chitosan, dendrimers, multi-arm polyethylene glycol (PEG), and hyaluronic acid (HA) [32,33]. HA is a naturally-occurring glycosaminoglycan and a major component of the extracellular matrix.…”

Polymer conjugates for focal and targeted delivery of drugs

“…Several polysaccharides are being used as polymeric carriers . Among natural and semi‐synthetic polysaccharides, hyaluronic acid, chitosan, and dextran have been largely investigated for drug bioconjugation .…”

“…Dextran is a natural polysaccharide containing monomers of the simple sugar glucose. This polyglucose biopolymer is characterized by α ‐1,6 linkages, with hydroxylated cyclohexyl units . Dextran has been particularly popular owing to its clinical approval for use as a plasma expander.…”