Table 3.

Novel delivery systems of triptolide

Delivery system	Excipients	Administration route	Animals	Dose of triptolide	Advantages	References
Hydrogel-thickened microemulsion	Carbomer 940, isopropyl myristate, Tween 80, propylene glycol, triethanolamine, menthol and water	Transdermal administration	New Zealand rabbits	1.2 mg/kg (acute toxicity study), 0.06–0.54 mg/kg (long-term toxicity study)	No obvious toxicities were observed in a series of toxicity tests, only mild reversible skin irritation signs were observed on the skin of animals	[134]
			Kunming mice and beagle dogs	0.03–0.27 mg/kg
			English guinea pigs	0.006 mg/kg (3 × 3 cm2 skin)
Microemulsion-based hydrogel	Poloxamer 407, oleic acid, Gemseal 40, Labrasol, Tween 80, ethanol and water	Transdermal administration	Rabbits	0.24 mg (3 × 3 cm2 skin)	It afforded a better sustained release profile and strong permeability with low irritation when compared to microemulsions	[135]
Liposome hydrogel patch	Egg lecithin, cholesterol, Viscomate NP-700, glycine aluminum, polyvinylpyrrolidone K-90, glycerin, tartaric acid and water	Transdermal administration (after treated with microneedles)	Male SD rats	1.6, 10, 20, 40 mg/kg	It provided a more stable and long-term release of triptolide compared with intragastric administration and had significant efficacy in CIA model	[137]
Solid lipid nanoparticles	Glyceryl monostearate, soybean phospholipid, acetone, Poloxamer 188, Tween 80 and water	Intragastrical administration	Male SD rats	0.45 mg/kg	SLNs had a protective effect against triptolide-induced male reproductive toxicity due to lower concentrations in testicular tissue	[140]
Solid lipid nanoparticles	Polyoxyl 40 hydrogenated castor oil, glyceryl behenate, diethylene glycol monoethyl ether, egg lecithin and water	Intragastrical administration	Male SD rats	1.0 mg/kg	SLNs alleviated the irritation in rat stomach tissues induced by triptolide, which could be attributed to reduced lipid peroxidation levels and inflammation of the stomach mucosa	[110]
Solid lipid nanoparticles	Tristearin glyceride, Poloxamine 908, soybean lecithin and water	Intragastrical administration	Male Wistar rats and male Kunming mice	0.2, 0.4 mg/kg	SLNs increased the anti-inflammatory activity of triptolide and reduced triptolide-induced hepatotoxicity	[141]
Nanostructured lipid carriers	Compritol 888 ATO, Capryol 90, Tween 80, Transcutol HP, soybean oil and water	Transdermal administration	Male SD rats	9.3 mg/kg	NLCs could effectively penetrate into skin for alleviating knee joint swelling and inhibiting inflammatory infiltration in RA rat model.	[143]
Lyotropic liquid crystals	Phytantriol, carbitol, vitamin E acetate and water	Transdermal administration	SD rats	0.08 mg/kg	Triptolide-loaded cubic and hexagonal liquid crystals presented excellent anti-arthritic effects with no obvious toxicity	[146]
Polymeric micelles	Methoxypolyethylene glycol–poly(D,L-lactic acid)-block copolymer	Intravenous administration	Kunming mice	0.51–1.25 mg/kg	Its acute and subacute toxicities were slighter than free triptolide owing to the sustained release characteristics and anti-lipid oxidative damage	[85]
			Wistar rats	0.1, 0.3 mg/kg
Polymeric vesicles	Poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer	Intravenous administration	C57/B6 mice	0.5 mg/kg	It increased the survival rate of mice and reduced the damage of free TP on the liver, kidney, and spleen	[147]
Polymeric nanoparticles	Poly-γ-glutamic acid-grafted di-tert-butyl L-aspartate hydrochloride	Intravenous administration	C57BL/6 mice	0.15 mg/kg	It could accumulate in the inflammatory joints of TNFα-Tg mice by EPR effect, with decreased death rate and toxicity at the liver and spleen induced by triptolide	[149]
Polymeric nanoparticles	Galactosyl-dextran-retinal conjugates	Intravenous administration	Male Balb/c mice	0.04 mg/kg	It preferentially accumulated in the inflamed joints through active targeting in CIA mice, thus reducing systemic toxicity	[150]