Table 3 Novel delivery systems of triptolide

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]