Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
Int J Pharm. 2011 Jul 29;414(1-2):298-311. doi: 10.1016/j.ijpharm.2011.05.006. Epub 2011 May 11.
Three amphiphilic random copolymers poly(2-(dimethylaminoethyl)methacrylate-co-alkylacrylate) (where, alkyl = hexyl, octyl, dodecyl) with 16 mol% hydrophobic substitution were synthesized. Surface tension, viscosity, fluorescence probe, dynamic light scattering (DLS), as well as transmission electron microscopic (TEM) techniques were utilized to investigate self-assembly formation by the hydrophobically modified polymers (HMPs) in pH 5. Formation of hydrophobic domains through inter-polymer chain interaction of the copolymer in dilute solution was confirmed by fluorescence probe studies. Average hydrodynamic diameter of the copolymer aggregates at different polymer concentration was measured by DLS studies. The copolymer with shorter hydrophobic chain exhibits larger hydrodynamic diameter in dilute solution, which decreased with either increase of concentration or increase of hydrophobic chain length. TEM images of the dilute solutions of the copolymers with shorter as well as with longer hydrophobic chain exhibit spherical aggregates of different sizes. The antimicrobial activity of the copolymers was evaluated by measuring the minimum inhibitory concentration value against one Gram-positive bacterium Bacillus subtilis and one Gram-negative bacterium Escherichia coli. The copolymer with the octyl group as pendent hydrophobic chain was found to be more effective in killing these microorganisms. The interaction of the cationic copolymers with calf-thymus DNA was studied by fluorescence quenching method. The polymer-DNA binding was found to be purely electrostatic in nature. The hydrophobes on the polymer backbone were found to have a significant influence on the binding process. Biocompatibility studies of the copolymers in terms of cytotoxicity measurements were finally performed at different concentrations of the HMPs to evaluate their potential application in biomedical fields.
合成了三种具有 16mol%疏水取代的双亲随机共聚物聚[2-（二甲氨基）乙基甲基丙烯酸酯-共-烷基丙烯酸酯]（其中，烷基=己基、辛基、十二烷基）。利用表面张力、粘度、荧光探针、动态光散射（DLS）以及透射电子显微镜（TEM）技术研究了疏水性修饰聚合物（HMP）在 pH 5 下的自组装形成。通过荧光探针研究证实了共聚物在稀溶液中通过聚合物链间相互作用形成疏水区。通过 DLS 研究测量了不同聚合物浓度下共聚物聚集体的平均水动力直径。在稀溶液中，疏水性较短的共聚物表现出较大的水动力直径，随着浓度或疏水性链长的增加而减小。具有较短和较长疏水性链的共聚物稀溶液的 TEM 图像显示出不同大小的球形聚集体。通过测量对革兰氏阳性菌枯草芽孢杆菌和革兰氏阴性菌大肠杆菌的最小抑菌浓度值，评估了共聚物的抗菌活性。发现带有辛基作为悬垂疏水性链的共聚物在杀死这些微生物方面更有效。通过荧光猝灭法研究了阳离子共聚物与小牛胸腺 DNA 的相互作用。发现聚合物-DNA 结合具有纯粹的静电性质。聚合物主链上的疏水基团对结合过程有显著影响。最后，根据不同浓度的 HMP 进行了共聚物的细胞毒性测量的生物相容性研究，以评估它们在生物医学领域的潜在应用。
