Nimodipine/ligustrazine double-load PLGA nanoparticles and preparation method thereof

Abstract

The invention relates to nimodipine / ligustrazine double-load PLGA nanoparticles which are prepared through a method comprising the steps that: nimodipine, ligustrazine phosphate and a polylactic acid-glycolic acid copolymer are precisely weight according to a mass ratio of 1:5-20:40-60; the materials are dissolved into acetone, such that an organic phase is obtained; a PVA water solution with a mass concentration of 0.5-1.0% is adopted as an aqueous phase; under stirring, the organic phase is slowly dropped into the aqueous phase; when dropping is finished, the mixture is continued to be stirred for 2-4h under a constant temperature of 40-50 DEG C, such that the organic solvent is volatilized; centrifugation is carried out; a sediment is washed 2-3 timed by using distilled water, and is lyophilized, such that the nimodipine / ligustrazine double-loading PLGA nanoparticles are obtained. According to the invention, PLGA is adopted as a carrier material, and P-gp inhibitors TMP and NMD are applied in combination, such that NMD / TMP-PLGA-NPs are prepared. Therefore, defects of short drug half-life, easy generation of cytotoxicity, and the like of simple combination are avoided, a P-gp efflux effect is inhibited, and NMD distribution to tissues is promoted. Therefore, the nanoparticles have certain advantages over single-load nanoparticles.

Description

(1) Technical field [0001] The invention relates to a nimodipine / ligustrazine double drug-loaded PLGA nanoparticle (NMD / TMP-PLGA-NPs) and a preparation method thereof. (2) Background technology [0002] Nimodipine (NMD) is a class of dihydropyridine calcium antagonists, which treat cerebrovascular diseases by dilating cerebral arterioles and increasing intracerebral blood flow. However, NMD is poorly water-soluble, and the commercially available NMD injection mainly dissolves the drug through ethanol, which is irritating to a certain extent; the clinically used NMD oral preparation has a short biological half-life, strong first-pass effect, and a bioavailability of only 5% to 13%; At the same time, as a substrate of P-glycoprotein (P-gp), NMD is easily affected by the efflux of P-gp on the blood-brain barrier (BBB), resulting in a low concentration in the brain, which limits its use in the brain. Therapeutic effect in the onset of cerebrovascular disease. Ligustrazine (Tet...

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Problems solved by technology

Therefore, the combination of TMP and NMD is expected to increase the concentration of NMD in the brain, but the simple combination of NMD and TMP still has the problem of short half-life of the drug and frequent administration, and too high a concentration of TMP in a short period of time may lead to too high a concentration of NMD in the brain , is toxic to normal cells or tissues

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