PH-sensitive targeted LPNs (lipid poly-L-histidine hybrid nanoparticles) for encapsulating anti-tumor drugs
A polyhistidine-targeted phospholipid technology, which is applied in antineoplastic drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of low cell entry efficiency and ineffective release of drugs in cells
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Embodiment 1
[0052] The preparation of the blank LPNs of embodiment 1
[0053]LPNs were prepared by a one-step precipitation method. A certain amount of polyhistidine (synthesized by Qiangyao Biotechnology Co., Ltd., molecular weight 3000, 4.1 mg) was precisely weighed and dissolved in anhydrous dimethyl sulfoxide solution, stirred for 2 hours, and used as the organic phase. Weigh a certain proportion of egg yolk lecithin (EPC, pharmaceutical grade, Shanghai Everett Pharmaceutical Technology Co., Ltd.) and phospholipid-PEG (DSPE-PEG, ≥98%, Shanghai Everett Pharmaceutical Technology Co., Ltd.) (the molar ratio is 1:3, 2.2g and 3.3g respectively, PEG molecular weight is 2000) in 2mM borax solution in 4% ethanol, stirred in a water bath at 65°C, as the water phase. Subsequently, the organic phase was dropped into the water phase under high-speed stirring (800-1200 rpm, preferably 1000 rpm), the water bath was removed, and the mixture was slowly lowered to room temperature and continued to st...
Embodiment 2
[0056] Example 2 Preparation of LPNs loaded with doxorubicin (DOX)
[0057] LPNs were prepared by a one-step precipitation method. Accurately weigh DOX (1 mg) and polyhistidine (molecular weight 3000, 4.1 mg) and dissolve them in anhydrous dimethyl sulfoxide solution respectively, add triethylamine in a molar ratio of 1:3 to DOX for 2 h to alkalinize. Then the two were mixed and stirred for 2h as the organic phase. Weigh a certain proportion of EPC and DSPE-PEG (the molar ratio is 1:3, respectively 2.2g and 3.3g, and the molecular weight of PEG is 2000) in 2mM borax solution of 4% ethanol, stir in a water bath at 65°C, as water Mutually. Subsequently, the organic phase was dropped into the water phase under high-speed stirring (800-1200 rpm, preferably 1000 rpm), the water bath was removed, and the mixture was slowly lowered to room temperature and continued to stir for 2 h. Finally, put it into a dialysis bag (3500kDa) and place it in 2mM borax dialysate, and replace the d...
Embodiment 3
[0058] Example 3 Preparation of LPNs loaded with docetaxel (PTX)
[0059] Accurately weighed PTX (1 mg) and polyhistidine (molecular weight 3000, 4.1 mg) were dissolved in DMSO solution and stirred for 2 h as the organic phase. Weigh a certain proportion of EPC and DSPE-PEG (the molar ratio is 1:3, respectively 2.2g and 3.3g, and the molecular weight of PEG is 2000) in 2mM borax solution of 4% ethanol, stir in a water bath at 65°C, as water Mutually. Subsequently, the organic phase was dropped into the water phase under high-speed stirring (800-1200 rpm, preferably 1000 rpm), the water bath was removed, and the mixture was slowly lowered to room temperature and continued to stir for 2 h. Finally, put it into a dialysis bag (3500kDa) and place it in 2mM borax dialysate, and replace the dialyzed fluid at room temperature for 1h, 2h, 4h, 8h, and 12h. The solution obtained in the dialysis bag is the prepared LPNs solution. Store in a refrigerator at 4°C for use: measure the par...
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