Co-loading micelles of ROS producers and oxidative response antineoplastic prodrugs and application thereof
An anti-tumor drug and anti-tumor drug technology is applied to the construction of co-loaded micelles of ROS generator lapaquinone and paclitaxel prodrug, and its application in drug delivery can solve problems such as toxic side effects and limited application, etc. To achieve the effect of low toxicity and side effects, efficient encapsulation and good stability
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0055] Embodiment 1: Synthesis of paclitaxel-linoleic acid small molecule prodrug (PTX-S-LA) bridged by monosulfide bridge
[0056] Add an appropriate amount of ethylene glycol into a 50mL three-neck flask, add a small amount of p-toluenesulfonic acid, heat to 110°C, slowly drip the oleic acid dissolved in toluene into the reaction flask, react for 2 hours, and monitor the reaction process by thin-layer chromatography , and then 20 mL of toluene was added to the system three times, and vacuum distillation was carried out to dryness. Dissolve the obtained product in 30mL of dichloromethane, add appropriate amount of thiodiacetic anhydride and a small amount of triethylamine, HOBT, EDCI, stir at room temperature for 24 hours, monitor the reaction process by thin layer chromatography, and purify by silica gel column chromatography An intermediate product is obtained. Finally, the intermediate product, EDCI, HOBt and DMAP were dissolved in 50 mL of anhydrous dichloromethane, ice-...
Embodiment 2
[0059] Embodiment 2: the synthesis of paclitaxel-linoleic acid small molecule prodrug (PTX-LA) directly linked by ester bond
[0060] Weigh an appropriate amount of paclitaxel into the flask, add a small amount of dichloromethane and stir until completely dissolved, add dropwise the linoleic acid solution pre-dissolved in dichloromethane, after mixing evenly, slowly add the dichloromethane solution of DMAP and DCC successively, avoiding Light reaction 48h. Filtration, concentration under reduced pressure, separation and purification of the preparative liquid phase to obtain the product. The above reactions are all in N 2 under protection.
[0061] The structure of the prodrug in Example 2 was determined by mass spectrometry and hydrogen nuclear magnetic resonance spectroscopy, and the results are shown in Figure 2. The solvent used for NMR was CDCl 3 , the spectral analysis results are as follows:
[0062] 1H NMR (600MHz, CDCl 3 ):δ8.08(t,2H),7.66(m,1H),7.53(m,3H),7.42(d...
Embodiment 3
[0063] Example 3: Optimization of preparation method of lapachone and paclitaxel prodrug co-loaded micelles
[0064] In this example, three different methods were used to prepare lapaquinone and paclitaxel prodrug co-loaded micelles, and the optimal preparation method was obtained through comparison.
[0065] Thin film dispersion method: Accurately weigh 4 mg of paclitaxel prodrug (PTX-S-LA or PTX-LA), 2.25 mg of lapachone, and 20 mg of PEG-PDLLA, dissolve in 6 ml of acetonitrile, remove the organic solvent by rotary evaporation, add normal saline water The probe was sonicated for 5 minutes, and the unencapsulated free drug, that is, the co-loaded micelles of dexaquinone and paclitaxel prodrug was removed by the filter membrane.
[0066] Dialysis method: Accurately weigh 4 mg of paclitaxel prodrug (PTX-S-LA or PTX-LA), 2.25 mg of lapachone, and 20 mg of PEG-PDLLA, dissolve them in 5 mL of N,N'-dimethylformamide (DMF), Then transfer the DMF solution of the polymer into a dialy...
PUM
| Property | Measurement | Unit |
|---|---|---|
| Particle size | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More