Table 2:

Overview of polysaccharide particle-based drug delivery systems

Polysaccharide	Type of delivery system	Drug	Modification and benefit	Source	Reference
Chitosan	Polyelectrolyte hydrogel Charge tuned to bind drugs Stabilisation of labile drugs in gastric conditions Chitosan provides mucosal binding and transmucosal transport	Doxorubicin DNA/RNA Therapeutic peptides and proteins	Gelation with polysaccharide anions Hyaluronic acid surface for cancer cell targeting	N-Deacetylated chitin from shells of arthropods	(Boddohi et al., 2009; Bodnar et al., 2005; Chen et al., 2003; Cui & Mumper, 2001; Deng et al., 2014; Goycoolea et al., 2009; Huang et al., 2014; Li et al., 2007; Ramasamy et al., 2013; Sarmento et al., 2006b Feng, 2015 #143)
	Ionic crosslinking Ammonium groups promote transmucosal delivery	Model macromolecule therapeutics Triclosan Furosemide Doxorubicin	Crosslinking with tripolyphosphate Amine conversion to quaternary ammonium groups to enhance stability in neutral conditions Hydroxypropylcyclodextrin for hydrophobic drug stabilisation Coating with anionic polysaccharides to stabilise particles and reduce cytotoxicity		(Amidi et al., 2006; Feng et al., 2015; Liu et al., 2008; Maestrelli et al., 2006; Sandri et al., 2007; Schütz et al., 2011)
	Tunable size drug delivery particles		Crosslinked by peptide coupling to multi-carboxylic acid compounds		(Bodnar et al., 2005)
Hyaluronic Acid	Amphiphilic self-assembly Target cancer cells	Etoposide Salinomycin Curcumin Doxorubicin Paclitaxel	Hydrophobic modification can bind cell membrane and unpack hydrogel Chitosan external layer to promote mucoadhesion	Part of animal cell extracellular matrix	(Huang et al., 2014; Park et al., 2012; Tripodo et al., 2015; Wei et al., 2013; Yang et al., 2011)
	Polyelectrolyte hydrogel Target cancer cells	Doxorubicin MicroRNA	Gelation with chitosan Hyaluronic acid surface for cancer cell targeting		(Deng et al., 2014; Ramasamy et al., 2013)
Hyaluronic acid	Covalently crosslinked biodegradable hydrogel	Therapeutic peptides and proteins	Crosslinking groups Methacrylate/dithiothreitol Maleimide and furan	Part of animal cell extracellular matrix	(Hirakura et al., 2010; Tan et al., 2011a)
Dextran	Modified for polyelectrolyte hydrogel Charge tuned to bind drugs	Doxorubicin Therapeutic peptides and proteins	Sulfate group added to make anionic polysaccharide	Bacteria synthesise from sucrose	(Chen et al., 2003; Huh et al., 2017; Ramasamy et al., 2013; Sarmento et al., 2006b)
	Modified for amphiphilic self-assembly Covalently bound drugs	Doxorubicin Bortezomib Curcumin	Modified with drug to make amphiphile for self-assembly Acid labile links Redox sensitive link through disulfide bridge		(Liu et al., 2013; Xu et al., 2015a; Xu et al., 2015b)
Arabinogalactan	Self-assembled particles Binds asialoglycoprotein receptors Targets liver and cancer tumors	Norcantharidin	Arabinogalactan, modified chitosan and drug self-assembled together into nanoparticles	Microbes and plants such as larch tress	(Caliceti et al., 2009; Dion et al., 2016; Zhang et al., 2018)
Starch	Hydrophobic modification binds and stabilises hydrophobic drugs	Flufenamic acid Testosterone Caffeine	Hydrophobically modified with propyl groups for self-assembly into nanoparticles	Energy storage in many green plants	(Robyt, 2008; Santander-Ortega et al., 2010)
•  Cyclodextrin From enzymatic degradation of starch	Hydrophobic cavity incorporated into a range of drug delivery vehicles	Co-loading of ciprofloxacin and 3-methyl benzoic acid Triclosan Furosemide Retinoic acid	Chemically crosslinked into dextran, agar and hydroxypropyl methyl cellulose hydrogels Non-covalent association with chitosan / tripolyphosphate ionic crosslinked system.		(Blanco-Fernandez et al., 2011; Caliceti et al., 2009; Maestrelli et al., 2006; Moya-Ortega et al., 2012; Peng et al., 2010)
•  Cyclodextrin From enzymatic degradation of starch
•  Cycloamylose From enzymatic degradation of starch	Amphiphilic self-assembly Binding to RNA for tumor delivery	siRNA shRNA	Cycloamylose modified with both cholesteryl and spermine groups for self-assembly into particles capable of binding RNA		(Fujii et al., 2014)
Pullulan	Amphiphilic self-assembly Binds and protect hydrophobic drugs and dyes	Model protein IRDye 800	Hydrophobic modification with cholesteryl groups	Converted from starch by fungus	(Singh et al., 2017). (Akiyoshi et al., 1991; Morimoto et al., 2013; Noh et al., 2012)
	PEI modification assembles into particles Targeting to asialoglycoprotein receptors in the liver	siRNA	Modified with PEI for DNA binding and protection		(Kang et al., 2010)
Inulin	Semi-crystalline inulin microparticles Tropism towards monocytes proposed for targeted drug delivery		Self-assembled under specific conditions and attached to drugs through bio-labile linkages	Compositae family plants	(Stevens et al., 2001; Wang et al., 2017)
	Inulin hydrogels deliver drugs to the colon Degraded by gut bacteria	Diflunisal 5-Fluorouracil	Modified with methacryl groups - crosslinked directly or through diacrylate linkers Succinyl groups added reduce swelling and degradation in stomach		(Castelli et al., 2008; Pitarresi et al., 2012; Vervoort et al., 1998a)
Cellulose	Covalently crosslinked hydrogel with redox sensitive linkages		Hydroxylpropyl cellulose modified and crosslinked with dithiol linkages	Structural component of many plants	(Rahimian et al., 2015; Senna et al., 2014; Tan et al., 2011b)
	Covalently crosslinked hydrogel with redox sensitive linkages Delivered to tumors through enhanced permeability and retention effect	Doxorubicin	Carboxymethyl cellulose crosslinked with cystamine bisacrylamide to form nanohydrogels		(Qian et al., 2014)
Hemicellulose	Polyelectrolyte hydrogels	Model protein	Carboxymethyl modification followed by gelation with chitosan	In cell walls of trees and grasses	(Du et al., 2004)
Alginic Acid	Ionic crosslinking Sustained release vehicle with retained charge to bind drugs	Doxorubicin Therapeutic proteins	Self-assembly with calcium ions Chitosan coatings and co-assembly to improve mucoadhesion and stability	Brown seaweed	(Elzatahry et al., 2009; Lee et al., 2013; Pawar & Edgar, 2012; Sarmento et al., 2006a; Xue et al., 2015)
	Polyelectrolyte hydrogel Charge tuned to bind drugs	Isoniazid, rifampicin, pyrazinamide	Gelation with chitosan		(Li et al., 2007; Zahoor et al., 2005)
Chondroitin Sulfate	Amphiphilic self-assembly Binds and stabilises hydrophobic drug Binding to cancer cells through receptors	Doxorubicin	Hydrophobic modification with acetate groups for self-assembly into particles	Component of animal cartilage	(Park et al., 2010; Shi et al., 2014)
Heparin	Polyelectrolyte hydrogel Target cancer cells	Model protein Paclitaxel	Gelation with chitosan	Secreted by mast cells	(Yang et al., 2015b) (Boddohi et al., 2009; Liu et al., 2007; Yuk et al., 2012)
	Amphiphilic self-assembly Covalently bound drugs Targeted to tumors using heparin	Dexamethasone Doxorubicin	Modified with drug to make amphiphile for self-assembly Acid labile links		(Li et al., 2014)
	Covalently crosslinked hydrogel with redox sensitive linkages	Doxorubicin	Methacrylate modified heparin crosslinked with cystamine bisacrylamide to form nanohydrogels		(Wu et al., 2015)
Gums •  Pectin	Oral delivery to colon Degraded by gut bacteria	Protein and polypeptide drugs	Self-assembly with calcium ions to resist solvation	Higher plant cell walls, especially fruits and vegetables	(Sirisha & D’Souza, 2016) (Izydorczyk, Ciu & Wang, 2005)
•  Gum Arabic	Biphasic emulsion supporting hydrophobic drugs	Metronidazole	Gelation of surfactant supported oil in water emulsion	Acacia Senegal	(Sahoo et al., 2015; Sirisha & D’Souza, 2016)