~1H-NMR法测定单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒的表面单甲氧基聚乙二醇含量及链密度

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目的采用1H-NMR定量地测定单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒(MePEG-PLGA-NP)表面单甲氧基聚乙二醇(MePEG)的含量及链密度,并研究了不同相对分子质量及不同比例的单甲氧基聚乙二醇对单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒表面的物理化学性质影响。方法以单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物(MePEG-PLGA)为载体,自乳化溶剂扩散法制备了聚乙二醇化聚乳酸-羟基乙酸纳米粒,并对其平均粒径和Zeta电位进行表征。1H-NMR用于确定单甲氧基聚乙二醇-聚乳酸-羟基乙酸的结构组成并测定了单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒表面的单甲氧基聚乙二醇的含量及链密度,并与比色法进行比较。结果单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物共聚物的结构组成与标示量基本一致;聚乙二醇的相对分子质量相同时,随着单甲氧基聚乙二醇比例的增加,单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒的平均粒径逐渐减小,Zeta电位的绝对值也逐渐减小,粒子表面的单甲氧基聚乙二醇含量(α)逐渐增加,其表面单甲氧基聚乙二醇的链密度(δ)逐渐增大,相邻两单甲氧基聚乙二醇分子链间的距离(D)逐渐减小;相同比例,随着单甲氧基聚乙二醇链长度的增加,单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒的平均粒径与Zeta电位都无明显差别,而α逐渐增加,δ逐渐减小,D逐渐增大;同种单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒,比色法测定的α值比1H-NMR测定的值偏高。结论1H-NMR能够定量地测定单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒表面的单甲氧基聚乙二醇含量及链密度;与比色法相比,1H-NMR测定的粒子表面单甲氧基聚乙二醇的含量更准确;实验范围内,单甲氧基聚乙二醇的相对分子质量和比例可以对纳米粒的平均粒径,Zeta电位和表面单甲氧基聚乙二醇含量及链密度等物理化学性质产生影响。 OBJECTIVE To quantitatively determine the content of monomethoxy polyethylene glycol (MePEG) on surface of monomethoxy polyethylene glycol-polylactic acid-glycolic acid copolymer nanoparticles (MePEG-PLGA-NP) The effects of different molecular weights and different ratios of monomethoxypolyethylene glycol on the physico-chemical properties of monomethoxy polyethylene glycol-poly (DL-lactide-co-glycolide) nanoparticles were studied. Methods Polyethylene glycollated poly (lactic-co-glycolic acid) nanoparticles were prepared by self-emulsifying solvent diffusion method using monomethoxy polyethylene glycol-polylactic acid-glycolic acid copolymer (MePEG-PLGA) as carrier. Path and zeta potential characterization. 1H-NMR was used to confirm the structure of the monomethoxy polyethylene glycol-polylactic acid-glycolic acid and to measure the monomethoxy group on the surface of the monomethoxy polyethylene glycol-polylactic acid-glycolic acid copolymer nanoparticles Polyethylene glycol content and chain density, and compared with the colorimetric method. Results Monomethoxy polyethylene glycol - polylactic acid - glycolic acid copolymer copolymer structure and marking the same amount; the same relative molecular mass of polyethylene glycol, with the proportion of monomethoxy polyethylene glycol , The average particle size of monomethoxy polyethylene glycol-poly (lactic-co-glycolic acid) copolymer nanoparticles decreased gradually and the absolute value of Zeta potential also decreased gradually. The monomethoxy polyethylene glycol The content (α) increased gradually, and the chain density (δ) of monomethoxypolyethylene glycol gradually increased. The distance (D) between adjacent two monomethoxypolyethylene glycol chains gradually decreased. In the same proportion, with the increase of monomethoxy polyethylene glycol chain length, the average particle size of monomethoxy polyethylene glycol-polylactic acid-glycolic acid copolymer nanoparticles has no significant difference with Zeta potential, and α Δ gradually decreased, D gradually increased; the same monomethoxy polyethylene glycol - polylactic acid - glycolic acid copolymer nanoparticles, α value measured by colorimetry higher than the value of 1H-NMR determination . Conclusion 1H-NMR can quantitatively determine the content of monomethoxy polyethylene glycol and the chain density on the surface of monomethoxy polyethylene glycol-polylactic acid-glycolic acid copolymer nanoparticles. Compared with colorimetric method, 1H-NMR The content of monomethoxy polyethylene glycol on the surface of the particles was more accurate. In the experimental range, the relative molecular mass and proportion of monomethoxy polyethylene glycol could influence the average particle size, Zeta potential and surface single Oxyethylene glycol content and chain density and other physical and chemical properties have an impact.
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