Cremophor el

The rat PIPN model was established according to methods previously described [11 (link), 24 (link), 25 (link)]. Briefly, 6 mg/mL of pharmaceutical grade paclitaxel (Hospira Australia Pty. Ltd., Australia) was diluted with sterile 0.9% saline to 1 mg/mL and given at a dosage of 2 mg/kg intraperitoneally (i.p.) in a volume of 0.5 ml/250 g rat every other day for a total of four injections (days 1, 3, 5, and 7). Control animals received the same volume of sterile saline treatment.
For the study to investigate the vehicle effect of paclitaxel formulation, rats received an equivalent volume of the vehicle for paclitaxel, with proportional amounts of Cremophor EL (C875008, Macklin Inc., Shanghai, China) and 95% dehydrated ethanol diluted in sterile 0.9% saline (Cremophor EL/ethanol 1:1). Control rats received equal amount of saline injection (0.5 ml/250 g). Rats were observed carefully for any abnormal behavioral changes every day following the treatment.

Paclitaxel, succinate anhydride, 2,3,4,6-Tetra-O-benzyl-d-glucose, succinic anhydride, 4-dimethylaminopyridine (DMAP), dicyclohexylcarbodiimide (DCC), palladium on 10% activated carbon (10% Pd/C), chlorotriethylsilane (TESCl), tetrabutylammonium fluoride (TBAF), dichloromethane (DCM), tetrahydrofuran (THF), methanol (MeOH), acetic acid (AcOH), n-hexane (Hex), and ethyl acetate (EA) were purchased from Energy Chemicals (Shanghai, China). Cremophor EL, Tween-80 and PEG-400 were purchased from Macklin (Shanghai, China).
3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium romide (MTT), dimethyl sulfoxide (DMSO), and β-glucuronidase were purchased from Sigma Aldrich (St. Louis, MO, USA). Leibovitz’s medium (L-15 medium), fetal bovine serum (FBS), and Hank’s balanced salt solution (HBSS) were purchased from Gibco (New York, NY, USA), rabbit serum (RS) was purchased from BestBio (Shanghai, China).
NMR spectra were recorded on a Bruker AVANCE III HD 400MHz Digital NMR Spectrometer (Karlsruhe, Germany). ESI mass spectra were recorded on a Thermo Scientific TSQ Quantum^TM Access MAX Mass Spectrometer (Waltham, MA, USA). Optical Density (OD) of MTT assay was measured with a Bio-rad iMark 96-well plate reader (Hercules, CA, USA).