Functional pla-peg copolymers, the nanoparticles thereof, their preparation and use for targeted drug delivery and imaging
A nanoparticle and drug technology, applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, organic chemistry, etc., can solve the problem that the structure does not include targeting ligands, and achieve the effect of volume reduction
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Embodiment 1
[0318] Example 1: Preparation of precursors for the preparation of nanoparticles
[0319] Preparation 1: Synthesis of Compound of Formula (XII)
[0320] 1. Steps for the Synthesis of Mono-Alkyne Polyethylene Glycol (Preparation 1A)
[0321]
[0322] Experimental procedure :
[0323] Triethylene glycol (Sigma-Aldrich, 5620 mg, 37.4 mmol, 1 equiv) was dissolved in anhydrous THF (50 mL), and the resulting solution was cooled to 0 °C under dry conditions. Sodium hydride (988 mg, 1.1 equiv) was added slowly, followed by propyne bromide (80 wt % in toluene, 4360 μL, 1.1 equiv) dropwise. The reaction was stirred at room temperature for 12 hours under an inert atmosphere.
[0324] Approach:
[0325] THF was removed under reduced pressure, the residue was dissolved in dichloromethane (DCM) and washed several times with brine. The resulting organic layer was washed with magnesium sulfate (MgSO 4 ), filtered, concentrated under reduced pressure, and dried under vacuum. The ...
Embodiment 2
[0499] Example 2: Nanoparticle Formation
[0500] Nanoparticles were prepared according to the following protocol and by using the components and amounts listed in the table below.
[0501] General plan
[0502] 1 - Dissolve the copolymer or mixture of copolymers in an organic solvent (final aqueous polymer concentration varies between 1-40 mg / mL).
[0503] 2- The organic phase is mixed with an aqueous phase containing a stabilizer (concentration varying between 0.1% - 1% w / v) (aqueous / organic phase volume ratio varying between 2.5 and 5). For the preparation of nanoparticles using the emulsification and volume reduction technique, shake the mixture vigorously for 1 min using a vortex shaker to obtain an emulsion. The emulsion was sonicated (using a probe, times varied from 1-10 minutes).
[0504] 3-Removal of the organic phase by evaporation (under reduced pressure or airflow).
[0505] 4- Ultracentrifuge the nanoparticles at 30000g for 30 minutes.
[0506] 5 - Resuspe...
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