Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of Drug Loading on the Physicochemical Properties and Stability of Cationic Lipid-based Plasmid DNA Complexes

  • Jeong, Ui-Hyeon (Department of Physical Pharmacy, College of Pharmacy, Chungnam National University) ;
  • Jung, Ji-Hye (Department of Physical Pharmacy, College of Pharmacy, Chungnam National University) ;
  • Davaa, Enkhzaya (Department of Physical Pharmacy, College of Pharmacy, Chungnam National University) ;
  • Park, Se-Jin (Department of Physical Pharmacy, College of Pharmacy, Chungnam National University) ;
  • Myung, Chang-Seon (Department of Pharmacology, College of Pharmacy, Chungnam National University) ;
  • Park, Jeong-Sook (Department of Physical Pharmacy, College of Pharmacy, Chungnam National University)
  • Published : 2009.10.20
Download PDF
⟨ Previous Next ⟩

Abstract

Recently, co-delivery of drug and gene has been attempted for higher therapeutic effects of anticancer agents. In this study, cationic liposomes were prepared using 1,2-dioleoyl-3-trimethylammoniopropane (DOTAP) as a cationic lipid to investigate the effect of drug loading on the physicochemical characteristics of cationic liposomes/DNA complexes. The complex formation between cationic liposomes and negatively charged plasmid DNA was confirmed and the protection from DNase was observed. Particle size of complexes was reduced not by drug loading, but by the increased ratio of cationic lipid to plasmid DNA. Meanwhile, zeta potential of complex was increased by the addition of cationic liposomes to complexes and the effect of drug loading on the zeta potential was not much higher than on particle size. Gel retardation of complexes was indicated when the complexation weight ratios of cationic lipid to plasmid DNA were higher than 24:1 for drug free complexes and 20:1 for drug loaded ones, respectively. Agarose gel retardation showed the similar complexation between plasmid DNA and drug free liposomes or drug loaded liposomes. Both complexes protected plasmid DNA from DNase independent of complexation temperature. From the results, drug loading may affect not the complex formation of cationic liposomes and plasmid DNA, but the particle size of complex.

Keywords

References

  1. X. Gao, K.S. Kim and D. Liu, Nonviral gene delivery: what we know and what is next, AAPS J., 9, E92-104 (2007). https://doi.org/10.1208/aapsj0901009
  2. W.J. Choi and C.K. Kim, Recent advances and future strategy in gene delivery system, J. Kor. Pharm. Sci., 30, 1-12 (2000).
  3. H. Joensuu, K. Holli, M. Heikkinen, E. Suonio, A.R. Aro, P. Hietanen and R. Huovinen, Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial, J. Clin. Oncol., 16, 3720-3730 (1998). https://doi.org/10.1200/JCO.1998.16.12.3720
  4. J.O. Shaughnessy, D. Miles, S. Vukelja, V. Moiseyenko, J.P. Ayoub, G. Cervantes, P. Fumoleau, S. Jones, W.Y. Lui, L. Mauriac, C. Twelves, G. van Hazel, S. Verma and R. Leonard, Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results, J. Clin. Oncol., 20, 2812- 2823 (2002). https://doi.org/10.1200/JCO.2002.09.002
  5. J.D. McConnel, C.G. Roehrborn, O.M. Bautista, G.L. Andriole, C.M. Dixon and J.W. Kusek, H. Lepor, K.T. McVary, L.M. Nyberg Jr., H.S. Clarke, E.D. Crawford, A. Diokno, J.P. Foley, H.E. Foster, S.C. Jacobs, S.A. Kaplan, K.J. Kreder, M.M. Lieber, M.S. Lucia, G.J. Miller, M. Menon, D.F. Milam, J.W. Ramsdell, N.S. Schenkman, K.M. Slawin and J.A. Smith, The long-term effect of doxazosin, finasteride, combination therapy on the clinical progression of benign prostatic hyperplasia, New Engl. J. Med., 349, 2387-2398 (2003).⨀ ភ⨀ភ⨀ Âភ⨀Âភ⨀‐ᣂភ⨀ᣂភ⨀䄀돀检ភ⨀ꁢ잖⨀ꁢ잖⨀礀돐检ភ⨀壌ភ⨀壌ភ⨀夀댐⣂ភ⨀⥫̄؀褊돐⣀ភ⨀適?⨀適?⨀飅ភ⨀餂돐킿ʗ⨀킲ភ⨀／ࡇ⨀夂덐䀀߿￿̀ࠀࠀꌀ￿羜䥇ꘀ￿￿䥇꬀￿７䩇글耘䩇넀਀䩇됀刺￿缙䩇똀̀䩇렀ఀ耚䩇묀﫿￿：䩇븀Ѐ耛䩇뼀ఀ䩇섀ﯿ￿缜䩇쌀ｿ餜䩇쐀Ȁ€䩇저ﳿ￿ﾗ䩇준؀肘䩇쨀￿ﾘ䩇餂돀샂ភ⨀塨?⨀ʗ⨀トភ⨀椀대ᕖࠄ䐀Ȁꊟﺿ缀Ā삟? https://doi.org/10.1056/NEJMoa030656
  6. P. Duesberg, R. Li, R. Sachs, A. Fabarius, M. Upender and R. Hehlmann, Cancer drug resistance: the central role of the karyotype, Drug Resist. Updat., 10, 51-58 (2003). https://doi.org/10.1016/j.drup.2007.02.003
  7. R. Li, R. Hehlman, R. Sachs and P. Duesberg, Chromosomal alterations cause the high rates and wide ranges of drug resistance in cancer cells, Cancer Genet. Cytogenet., 163, 44-56 (2003). https://doi.org/10.1016/j.cancergencyto.2005.05.003
  8. R.A. Gjerset and D. Mercola, Sensitization of tumors to chemotherapy through gene therapy, Adv. Exp. Med. Biol., 465, 273-291 (2000). https://doi.org/10.1007/0-306-46817-4_24
  9. B.D. Lee, K.J. French, Y. Zhuang and C.D. Smith, Development of a syngeneic in vivo tumor model and its use in evaluating a novel P-glycoprotein modulator, PGP-4008, Oncol. Res., 14, 49-60 (2003). https://doi.org/10.3727/000000003108748603
  10. R. Koivusalo, E. Krausz, H. Helenius and S. Hietanen, Chemotherapy compounds in cervical cancer cells primed by reconstitution of p53 function after short interfering RNA mediated degradation of human Papilloma virus 18 E6 mRNA: opposite effect of siRNA in combination with different drugs, Mol. Pharmacol., 68, 372-382 (2005). https://doi.org/10.1124/mol.105.011189
  11. R.R. Nair, J.R. Rodgers and L.A. Schwarz, Enhancement of transgene expression by combining glucocorticoids and antimitotic agents during transient transfection using DNA-cationic liposomes, Mol. Ther., 5, 455-462 (2002). https://doi.org/10.1006/mthe.2002.0567
  12. F. Liu, L.M. Shollenberger and L. Huang, Non-immunostimulatory nonviral vectors, FASEB J., 18, 1779-1781 (2004).
  13. Y. Wang, S. Gao, W.H. Ye, H.S. Yoon, Y.Y. Yang, Co-delivery of drugs and DNA from cationic core-shell nanoparticles selfassembled from a biodegradable copolymer, Nat. Mater., 5, 791-796 (2006). https://doi.org/10.1038/nmat1737
  14. Y. Wang, L.S. Wang, S.H. Goh and Y.Y. Yang, Synthesis and characterization of cationic micelle self-assembled from a biodegradable copolymer for gene delivery, Biomacromolecules, 8, 1028-1037 (2007). https://doi.org/10.1021/bm061051c
  15. N. Wiradharma, Y.W. Tong and Y.Y. Yang, Self-assembled oligopeptide nanostructures for co-delivery of drug and gene with synergistic therapeutic effect, Biomaterials, 30, 3100-3109 (2009). https://doi.org/10.1016/j.biomaterials.2009.03.006
  16. J.W. Kang, E. Davaa, Y.T. Kim and J.S. Park, A new vaginal delivery system based on a dispersion of cationic liposomes in a thermosensitive gel for the controlled release of amphotericin B, J. Drug Target., submitted (2009).
  17. K.A. Min, S.K. Lee and C.K. Kim, Improved gene expression pattern using Epstein-Barr virus (EBV)-based plasmid and cationic emulsion, Biomaterials, 26, 1063-1070 (2004). https://doi.org/10.1016/j.biomaterials.2004.04.005