Drug delivery for bioactive polysaccharides to improve their drug-like properties and curative efficacy

Figures & data

Table 1. Drug delivery systems for bioactive polysaccharides to improve their drug-like properties and curative efficacy.

Name	Key properties	DDSs and achieved improvements
Ganoderma lucidum PS	A neutral heteroglycan composed of d-glucose, d-galactose, d-mannose, d-xylose, l-fucose, and l-rhamnose (5.35:2.67:1:1.19:0.38:0.37, molar ratio); MW, 37 kDa (Bao et al., 2002)	Liposome (in vitro; SC): improved immunoregulatory activities and adjuvanticity (Liu et al., 2015, 2016a,b)
Radix Ophiopogonis PS	A graminan-type fructan (a Fruf (2 → 1) backbone with a Fruf (2 → 6) Fruf (2 → branch per average 2.8 of main chain residues); MW, 4.8 kDa (PDI, 1.41) (Xu et al., 2005) IV: t1/2, ∼0.5 h; MRT, 0.65 h. Oral BA: 1.7% (rats) (Lin et al., 2010b)	Liposome (in vitro; SC or IM): improved immunoregulatory activities and adjuvanticity (Fan et al., 2014, 2015a, 2016a,b; Sun et al., 2016a) PEG-coated liposome (IV): 45-fold prolonged t1/2; improved targeting delivery (Wang et al., 2015) Mono-PEGylation (IV): 32- to 100-fold prolonged t1/2; improved targeting delivery, therapeutic effect, and administration compliance (Lin et al., 2011a,b; Sun et al., 2013) ISFS (SC): day(s)- to week(s)-long sustained delivery; improved administration compliance (Shi et al., 2015b; Wang et al., 2017) ISFS + MonoPEGylatin (SC): week(s)- to month(s)-long sustained delivery; improved administration compliance (Shi et al., 2014)
Astragalus PS	A (1 → 4)-linked dextran backbone with a (1 → 6)-linked branch every 10 residues; MW, 20.7 kDa (Niu et al., 2011)	Liposome (in vitro; SC): improved immunoregulatory activities and adjuvanticity (Fan et al., 2011, 2013a) ISFS (poloxamer-based): week-long sustained release; improved administration compliance (Yu et al., 2017)
Lycium barbarum PSs	A neutral heteroglycan composed of glucose, xylose, galactose, rhamnose, and mannose (49.8:31.3:9.3:7.5:6.4, molar ratio); MW, 24–241 kDa (Amagase et al., 2009; Wu et al., 2010)	Liposome (in vitro; SC): improved immunoregulatory activities and adjuvanticity (Bo et al., 2015, 2016)
Rehmannia glutinosa PS	An acidic PS composed of l-arabinose, d-galactose, l-rhamnose, and d-galacturonic acid (10:10:1:1 or 14:7:3:8, molar ratio); MW, 35.7 kDa (Tomoda et al., 1994; Tan et al., 2012)	Liposome (in vitro; SC): improved immunoregulatory activities and adjuvanticity (Huang et al., 2014, 2016)
Epimedium PS	An acidic PS composed of xylose, galactose, rhamnose, arabinose, and galacturonic acid (6.4:2.3:1.8:6.9:82.6, weight ratio); MW, 1.46 kDa (Li, 2005)	Liposome (in vitro): improved immunoregulatory activities; synergistic effects with propolis flavone (Fan et al., 2013b, 2015b)
Propylene glycol alginate sodium sulfate (Li et al., 2013)	A marine sulfated PS composed of β-d-mannuronic acid and α-l-guluronic acid; MW, 11 kDa (PDI, 1.6) IV: t1/2, 3.11 h; MRT, 2.59 h. Oral BA: 9.54% (rats)	PLGA nanoparticles: increased oral BA, 18.2% (rats); prolonged MRT, 84.7 h
Heparin	A highly sulfated glycosaminoglycans; MW, ∼15 kDa Injection: t1/2, ∼1.5 h (Kandrotas, 1992). Oral BA: hardly absorbed (Chen et al., 2009)	Positively charged nanoparticles (chitosan with a low MW of 30 kDa): increased oral BA, 20.5% (rats) (Chen et al., 2009)
Low-MW heparin	A highly sulfated glycosaminoglycans; MW, less than 8 kDa Injection: t1/2, 0.57–4 h (Samama & Gerotziafas, 2000; Hwang et al., 2012). Oral BA: hardly absorbed (Dong et al., 2007; Hwang et al., 2012; Alam et al., 2014); 1.6% (monkeys) and 7.4% (rats) (Alhilal et al., 2014)	Positively charged nanoparticles (poly(ε-caprolactone)/Eudragit^® RS,1:1): increased oral BA, 51–59% (rabbits); prolonged anticoagulant effect, 8–11.5 h (Hoffart et al., 2006) Conjugation (DA): increased oral BA, ∼16% (mice) (Dong et al., 2007) Conjugation (dimeric DA): increased oral BA, 19.3% (rats) (Hwang et al., 2012) Conjugation (T-DA): increased oral BA, 19.9% (monkeys) and 33.5% (rats) (Alhilal et al., 2014) Conjugation (T-DA)+complexation (DCEA): increased oral BA, 34.3% (rats); prolonged MRT, 7.5 h; improved anti-angiogenic efficacy (Alam et al., 2014)
Chinese yam PS	A neutral PS composed of glucose and galactose (1.52:1, molar ratio); MW, 16.6 kDa (Yang et al., 2015)	PLGA nanoparticles: slowed release and improved immunomodulatory activity in vitro (Luo et al., 2016)
Antrodia camphorate PS	A (1 → 3)-β-d-glucan; MW, >200 kDa (Kong et al., 2013)	Positively charged nanoparticles (chitosan with a MW of 200 kDa): improved anti-tumor efficacy in vitro (Chang et al., 2015)
Low MW chondroitin sulfate (Xiao et al., 2014)	A sulfated glycosaminoglycans; MW, 4.1 kDa Oral administration: t1/2, 5.9 h; AUC0–24 h, 55.2 mg/(L h) (rats)	Conjugation (α-linolenic acid): prolonged t1/2, 11.2–18.8 h; increased oral AUC0–24 h, 80.1–172.4 mg/(L h) (rats)

PS: polysaccharide; MW: molecular weight; PDI: polymer dispersity index; SC: subcutaneous injection; IV: intravenous injection; MI: intramuscular injection; t_1/2: plasma half-life; MRT: mean residence time; BA: bioavailability; AUC: area under the curve; PEG: polyethylene glycol; PLGA: poly(d,l-lactide-co-glycolide) copolymer; DA: deoxycholic acid; T-DA: tetrameric DA; DCEA: deoxycholylethylamine; ISFS: in situ forming system.

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