Structure of the Conjugated Linoleic Acid-Paclitaxel Conjugate Self-Assembled Nanoparticles
ZHENG Xiu-chai1a,1b, XU Mei-qi1a,1b, LIU Man1a,1b, ZHONG Ting1a,1b, HAO Yan-li1a,1b, ZHANG Shuang1a,1b, LI Zhan-tao1a,1b, LI Zhuo-yue1a,1b, DUAN Xiao-chuan1a,1b, FENG Zhen-han1a, WANG Jing-ru1a,1b, LI Hui1a, WANG Guang-xue1b, LIAO Ai1b, ZHANG Hua2, LIU Bi-lin3, ZHANG Xuan1a,1b*
1a. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems;1b. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; 2. Key Laboratory of Xinjiang Phytomedicine Resources and Utilization of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832000, China; 3. College of Pharmaceutical Engineering, Chongqing Chemical Industry Vocational College, Chongqing 401228, China
Abstract:OBJECTIVE To prepare, the conjugated linoleic acid-paclitaxel conjugate self-assembled nanoparticles (CLA-PTX NPs) by nanoprecipitation. METHODS The Dynamic light scattering, nuclear magnetic resonance spectroscopy, raman spectroscopy, fourier transform infrared spectroscopy and nitrogen element distribution of CLA-PTX NPs were studied. RESULTS The hydroxyl groups (C-4 and C-10 of PTX) and the acetyl groups (C-1 and C-7 of PTX) were on the surface of CLA-PTX NPs, CLA carbon chain, the benzene ring (C-2 and C-3′ of PTX) and the amide bond (C-3′ of PTX) were inside the CLA-PTX NPs. CONCLUSION It is speculated that the self-assembly of CLA-PTX is that the non-polar CLA carbon chain spontaneously aggregates inward due to hydrophobic interaction, and the hydrophilic oxygen-containing groups of PTX (hydroxyl group and carbonyl group) are on the surface of the nanoparticle to form nanoparticles.
RAWAL S, PATEL M M. Threatening cancer with nanoparticle aided combination oncotherapy[J]. J Controlled Release, 2019, 301: 76-109.
[2]
YOUN Y S, BAE Y H. Perspectives on the past, present, and future of cancer nanomedicine[J]. Adv Drug Deliv Rev, 2018, 130: 3-11.
[3]
EKLADIOUS I, COLSON Y L, GRINSTAFF M W. Polymer-drug conjugate therapeutics: advances, insights and prospects[J]. Nat Rev Drug Discov, 2019, 18(4):273-294.
[4]
FENG Q, TONG R. Anticancer nanoparticulate polymer-drug conjugate[J]. Bioeng Transl Med, 2016, 1(3):277-296.
[5]
CHEETHAM A G, CHAKROUN R W, MA W, et al. Self-assembling prodrugs[J]. Chem Soc Rev, 2017, 46(21):6638-6663.
[6]
KE X Y, ZHAO B J, ZHAO X, et al. The therapeutic efficacy of conjugated linoleic acid-paclitaxel on glioma in the rat[J]. Biomaterials, 2010, 31(22):5855-5864.
[7]
LI D, YANG K, LI J S, et al. Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings[J]. Int J Nanomed, 2012, 7: 6105-6114.
[8]
DU R, ZHONG T, ZHANG W Q, et al. Antitumor effect of iRGD-modified liposomes containing conjugated linoleic acid-paclitaxel (CLA-PTX) on B16-F10 melanoma[J]. Int J Nanomed, 2014, 9: 3091-105.
[9]
ZHONG T, YAO X, ZHANG S, et al. A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic[J]. Sci Rep, 2016, 6: 36614.
[10]
ZHONG T, HAO Y L, YAO X, et al. Effect of XlogP and hansen solubility parameters on small molecule modified paclitaxel anticancer drug conjugates self-assembled into nanoparticles[J]. Bioconjugate Chem, 2018, 29(2):437-444.
[11]
WANG L J, GENG H R, HU M F, et al.Determination of glucosamine hydrochloride in capsules by 1H-NMR method[J]. Chin Pharm J(中国药学杂志),2016,51(20):1781-1785.
[12]
HUANG R, YE X X, LU D, et al. Analysis of the polymorphism of furosemide by Raman spectroscopy and establishment of quantitative model [J]. Chin Pharm J(中国药学杂志), 2018,53(24):2127-2131.
[13]
MELLO D, NACUCCHI M, ANASTASI G, et al. New approach in auger elemental relative sensitive factor calculation by using TEM-EDS analysis based on bi-layers of pure elements[J]. Ultramicroscopy, 2018, 193: 143-150.
[14]
HARA T, TANAKA K, MAEHATA K, et al. Microcalorimeter-type energy dispersive X-ray spectrometer for a transmission electron microscope[J]. J Elec Microsc (Tokyo), 2010, 59(1):17-26.
[15]
FRIEL J J, LYMAN C E. X-ray mapping in electron-beam instruments[J]. Microsc Microanal, 2006, 12(1):2-25.