Xin Zhu

C ₂₄ H ₂₄ O ₆ S, triclinic, space group P 1̅ (no. 2), a = 10.9153(5) Å, b = 14.2225(8) Å, c = 15.5301(6) Å, α = 64.137(5)°, β = 80.402(4)°, γ = 87.791(4)°, V = 2137.5(2) Å ³ , Z = 4, T = 100 K.

C ₅₁ H ₇₀ O ₉ , triclinic, space group P 1 (no. 1), a = 7.67650(10) Å, b = 11.9494(2) Å, c = 13.8656(2) Å, α = 114.055(1) ^∘ , β = 103.568(1) ^∘ , γ = 93.456(1) ^∘ , V = 1111.46(3) Å ³ , Z = 1, T = 100(11) K.

C₄₄H₁₀₈N₂₀O₁₂S₄, monoclinic, P2₁/n (no. 14), a = 8.0480(3) Å, b = 18.6415(7) Å, c = 11.9008(4) Å, β = 103.242(2)°, V = 1737.97(11) ų, Z = 4, R_gt (F) = 0.0471, wR_ref (F ²) = 0.1422, T = 296(2) K.

Triptolide (TP) is a potential drug candidate for the treatment of cancer, but its use was hampered by its systemic toxicity and poor water solubility. Hence, a TP-CSO prodrug was synthesized by conjugating TP to chitosan oligosaccharide (CSO), and characterized by ¹H NMR, FTIR, DSC and XRD analyses. The TP-CSO containing about 4 wt% of TP exhibited excellent water solubility (15 mg/mL) compared to TP (0.017 mg/mL). Compared with TP, the pharmacokinetics of the conjugate after oral administration showed a three-fold increase in the half-life in the blood circulation and a 3.2-fold increase in AUC _(0–∞). The orally administered TP-CSO could more effectively inhibit tumor progression but with much lower systemic toxicity compared with TP, indicating significant potential for further clinical trials. In conclusion, CSO-based conjugate systems may be useful as a platform for the oral delivery of other sparingly soluble drugs.

C₂₆H₅₄N₁₀O₃S₃, monoclinic, Pc (no. 7), a = 8.5247(5) Å, b = 10.6658(5) Å, c = 21.2970(10) Å, β = 109.472(2)°, V = 1825.63(16) ų, Z = 2, R _gt(F) = 0.0366, wR _ref(F ²) = 0.0866, T = 298 K.

C₁₂H₁₈N₈O₄S₂, monoclinic, P2₁/c (no. 14), a = 13.378(4) Å, b = 5.0129(14) Å, c = 13.396(4) Å, β = 96.118(4)°, V = 893.3(4) ų, Z = 2, R _gt (F) = 0.0561, wR _ref (F ²) = 0.1201, T = 298 K.

C ₁₂ H ₂₀ N ₈ O ₆ S ₂ , monoclinic, P 2 ₁ / c (no. 14), a = 15.8571(11) Å, b = 7.6581(5) Å, c = 16.9166(12) Å, β = 113.334(1)°, V = 1886.3(2) Å ³ , Z = 4, R _gt ( F ) = 0.0317, wR _ref ( F ² ) = 0.1053, T = 298 K.

A new platform for triptolide (TP) delivery was prepared by conjugating TP to a carboxylmethyl chitosan (CMCS). Compared with the natural TP, the TP-conjugate (TP-CMCS) containing TP of ~5 wt% exhibited excellent aqueous solubility (>5 mg/mL). Results of in vitro experiments showed that TP-CMCS could relieve TP-induced inhibition on RAW264.7 cells and apoptosis, respectively. Compared with the TP group, TP-CMCS could effectively alleviate the toxicity injury of TP and decreased the mortality rate of the mice (p < 0.05). TP-CMCS did not cause much damage to the liver (AST and ALT) and kidney (BUN and CRE) (p < 0.05). After administration, the levels of IL-6, IL-1β, and TNF-α decreased, and the arthritis detumescence percentages increased significantly, and the bony erosion degree was distinctly decreased in the TP-CMCS groups and TP group. Our results suggested that TP-CMCS was a useful carrier for the treatment of RA, which enhanced aqueous solubility of free TP and reduced drug toxicity in vitro and in vivo.