Abstract:The study of the interaction between drugs and biomembrane is of great significance to the understanding of the drug efficacy and the improvment of their biological properties. However, the composition of biomembrane is complex, which makes it difficult to study the interaction between active components of drugs and biomembrane directly. We used liposome as mimetic biomembrane, investigated the interaction of evodiamine with liposome, analyzed the entrapment position of evodiamine among liposome, and the possible mechanism of the anti-inflammatory effect of evodiamine was also discussed. 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) has been used as membrane material in this study and liposomes containing different molar percentage of evodiamine (x) were prepared by thin-film dispersion method. Fourier transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC) were used to analyze the frequency and shape of infrared absorption peaks and the changes of the calorimetric parameters of DPPC molecules with the increasing of the molar percentage of drugs. The entrapment position of the evodiamine in liposome and the effect of this drug on the fluidity of liposome membrane were discussed. Data showed that the frequency of the asymmetric stretching vibration of the phosphate group in the DPPC head region hardly changed in the concentration range of 0<x<10 mol%, but the phase transition temperature and enthalpy of the liposome decreased with increasing x in this concentration range. In the concentration range of 0<x<5 mol%, the absorption wave number of hydrated carbonyl in the DPPC interface region increased from 1 726.0 to 1 731.8 cm-1, however, this wave number decreased to 1 728.0 cm-1 at x=10 mol%. In the concentration range of 10 mol%≤x<20 mol%, the wave number of asymmetric stretching vibration of phosphate group decreased from 1 242.0 to 1 236.3 cm-1, but the absorption frequency of hydrated carbonyl hardly changed, and the phase transition temperature and enthalpy of liposome increased with increasing x. The wave number of the symmetrical stretching vibration of methylene in pure DPPC liposomes was 2 848.4 cm-1, which increased to 2 850.3 cm-1 after drug loading. These results indicated that the entrapment location of evodiamine in liposomes is concentration-dependent: in the concentration range of 0<x<10 mol%, evodiamine molecules mainly incorporate into the hydrophobic region of DPPC molecules and a few locate at the interfacial region of DPPC molecules. In the range of 10 mol%≤x<20 mol%, evodiamine molecules mainly incorporate into the hydrophilic head region of the DPPC molecules and a few locate at the hydrophobic tail chain of DPPC molecules. The phase transition temperatures of all drug containing liposomes are lower than those of pure DPPC liposomes. That is to say, the membrane fluidity of the liposomes could be increased by different concentrations of evodiamine. Moreover, at x=10 mol%, the membrane fluidity of liposomes is the largest. This study will play an important role in the further investigation of the interaction mechanism of evodiamine with biomembrane.
[1] Chinese Pharmacopoeia Commission(中华人民共和国药典委员会). Pharmacopoeia of the People’s Republic of China, Part One(中华人民共和国药典一部). Beijing:China Medical Science Press(北京:中国医药科技出版社),2015.
[2] ZHANG Zhi-xian,JIANG Mei-ling,WANG Xin-hui,et al(张志仙,蒋美玲,王欣慧,等). Progress in Modern Biomedicine(现代生物医学进展),2014,14(21):4189.
[3] Sugimoto T,Miyase T,Kuroyanagi M,et al. Chemical and Pharmaceutical Bulletin,2011,36(11):4453.
[4] Huang X,Li W,Yang X W. Fitoterapia,2012,83(4):709.
[5] LU Shan-shan,JIANG Xiao-yan,GE Miao,et al(卢杉杉,姜晓燕,葛 苗,等). Pharmaceutical Biotechnology(药物生物技术),2014,(3):231.
[6] Nunes C,Brezesinski G,Lima J L,et al. Journal of Physical Chemistry B,2011,115(24):8024.
[7] Wei T T,Sun H Y,Deng G,et al. Journal of Thermal Analysis and Calorimetry,2018,132(1):685.
[8] Gmajner D,Ulrih N P. Journal of Thermal Analysis and Calorimetry,2011,106(1):255.
[9] Bakonyi M,Berkó S,Budai-Szücs M,et al. Journal of Thermal Analysis and Calorimetry,2017,130(7):1.
[10] Wu F G,Sun H Y,Zhou Y,et al. Rsc Advances,2014,4(93):51171.
[11] Manrique-Moreno M,Heinbockel L,Suwalsky M,et al. Biochimica Biophysica Acta-Biomembranes,2016,1858(9):2123.
[12] Lörincz A,Mihály J,Németh C,et al. Biochimica Biophysica Acta-Biomembranes,2015,1848(5):1092.
[13] Berényi S,Mihály J,Wacha A,et al. Colloids Surf B Biointerfaces,2014,118(22):164.
[14] Kamiński D M,Arczewska M,Pociecha D,et al. Journal of Molecular Structure,2015,1080:57.
[15] Wu F G,Jia Q,Wu R G,et al. Journal of Physical Chemistry B,2011,115(26):8559.
[16] Wu F G,Wang N N,Yu J S,et al. Journal of Physical Chemistry B,2010,114(6):2158.
[17] Bilge D,Kazanci N,Severcan F. Journal of Molecular Structure,2013,1040(20):75.
[18] Wu R G,Wang Y R,Wu F G,et al. Journal of Thermal Analysis and Calorimetry,2012,109(1):311.
[19] Berényi S,Mihály J,Kristyán S,et al. Biochimica Et Biophysica Acta-Biomembranes,2013,1828(2):661.
[20] Wu R G, Dai J D, Wu F G, et al. Int. J. Pharm., 2012,438(1-2): 91.
[21] Pili B, Bourgaux C, Amenitsch H, et al. Biochimica Biophysica Acta-Biomembranes, 2010, 1798(8):1522.
[22] Kalamkar V,Joshi M,Borkar V,et al. Bioorganic and Medicinal Chemistry,2013,21(21):6753.
[23] Nunes C,Brezesinski G,Lima J L F C,et al. Soft Matter,2011,7(6):3002.