Journal of Pharmaceutical Investigation

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

DOI QR Code

Preparation of Lipid Nanoparticles Containing Paclitaxel and their in vitro Gastrointestinal Stability

파클리탁셀을 함유한 지질나노입자의 제조와 인공 소화액에서의 안정성 평가

  • Kim, Eun-Hye (Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology) ;
  • Lee, Jung-Eun (Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology) ;
  • Lim, Deok-Hwi (Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology) ;
  • Jung, Suk-Hyun (Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology) ;
  • Seong, Ha-Soo (Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology) ;
  • Park, Eun-Seok (College of Pharmacy, Sungkyunkwan University) ;
  • Shin, Byung-Cheol (Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology)
  • 김은혜 (한국화학연구원 신약기반기술연구센터) ;
  • 이정은 (한국화학연구원 신약기반기술연구센터) ;
  • 임덕휘 (한국화학연구원 신약기반기술연구센터) ;
  • 정석현 (한국화학연구원 신약기반기술연구센터) ;
  • 성하수 (한국화학연구원 신약기반기술연구센터) ;
  • 박은석 (성균관대학교 약학대학) ;
  • 신병철 (한국화학연구원 신약기반기술연구센터)
  • Published : 2008.04.21
Download PDF
⟨ Previous Next ⟩

Abstract

Peroral administration is the most convenient one for the administration of pharmaceutically active compounds. Most of poorly water-soluble drugs administered via the oral route, however, remain poorly available due to their precipitation in the gastrointestinal (GI) tract and low permeability through intestinal mucosa. In this study, one of drug delivery carriers, lipid nanoparticles (LNPs) were designed in order to reduce side effects and improve solubility and stability in GI tract of the poorly water soluble drugs. However, plain LNPs are generally unstable in the GI tract and susceptible to the action of acids, bile salts and enzymes. Accordingly, the surface of LNPs was modified with polyethylene glycol (PEG) for the purpose of improving solubility and GI stability of paclitaxel (PTX) in vitro. PEG-modified LNPs containing PTX was prepared by spontaneous emulsification and solvent evaporation (SESE) method and characterized for mean particle diameter, entrapping efficiency, zeta potential value and in vitro GI stability. Mean particle diameter and zeta potential value of PEG-modified LNP containing PTX showed approximately 86.9 nm and -22.9 mV, respectively. PTX entrapping efficiency was about 70.5% determined by UV/VIS spectrophotometer. Futhermore, change of particle diameter of PTX-loaded PEG-LNPs in simulated GI fluids and bile fluid was evaluated as a criteria of GI stability. Particle diameter of PTX-loaded PEG-LNPs were preserved under 200 nm for 6 hrs in simulated GI fluids and bile fluid at $37^{\circ}C$ when DSPE-mPEG2000 was added to formulation of LNPs above 4 mole ratio. As a result, PEG-modified LNPs improved stability of plain LNPs that would aggregate in simulated GI fluids and bile solution. These results indicate that LNPs modified with biocompatible and nontoxic polymer such as PEG might be useful for enhancement of GI stability of poorly water-soluble drugs and they might affect PTX absorption affirmatively in gastrointestinal mucosa.

Keywords

References

  1. S.A. Wissing, O. Kayser and R.H. Müller, Solid lipid nanoparticles for parenteral drug delivery, Adv. Drug Deli. Rev., 56, 1257-1272 (2004) https://doi.org/10.1016/j.addr.2003.12.002
  2. M. Trotta, F. Debernardi and O. Caputo, Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique, Int. J. Pharm., 257, 153-160 (2003) https://doi.org/10.1016/S0378-5173(03)00135-2
  3. M. Rawat, D. Singh, S. Saraf and S. Safar, Nanocarriers: Promising vehicle for bioactive drugs, Biol. Pharm. Bull., 29, 1790-1798 (2006) https://doi.org/10.1248/bpb.29.1790
  4. W.R. Rerkins, I. Ahmad, X. Li, D.J. Hirsh, G.R. Masters, C.J. Fecko, J.K. Lee, S. Ali, J. Nguyen, J. Schupsky, C. Herbert, A.S. Janoff and E. Mayhew, Novel therapeutic nano-particles (lipocores): trapping poorly water soluble compounds, Int. J. Pharm., 200, 27-39 (2000) https://doi.org/10.1016/S0378-5173(00)00329-X
  5. G. Suresh, K. Manjunath, V. Venkateswarlu and V. Satyanarayana, Preparation, characterization, and in vitro and in vivo evaluation of lovastatin solid lipid nanoparticles, AAPS Pharm. Sci. Tech., 8(1) article 24 (2007)
  6. R.B. Greenwald, Y.H. Choe, J. McGuire and C.D. Conover, Effective drug delivery by PEGylated drug conjugates, Adv. Drug Deli. Rev., 55, 217-250 (2003) https://doi.org/10.1016/S0169-409X(02)00180-1
  7. C.M. Lee, H.C. Lee and K.Y. Lee, O-palmitoylcurdlan surface (OPCurS)-coated liposomes for oral drug delivery, J. Biosci. Bioeng., 100, 255-259 (2005) https://doi.org/10.1263/jbb.100.255
  8. A.K. Singla, A. Garg and D. Aggarwal, Paclitaxel and its formulations, Int. J. Pharm., 235, 179-192 (2002) https://doi.org/10.1016/S0378-5173(01)00986-3
  9. S.K. Kumar, S.A. Williams, J.T. Isaacs, S.R. Denmeade and S.R. Khan, Modulating paclitaxel bioavailability for targeting prostate cancer, Bioorg. Med. Chem., 15, 4973-4984 (2007) https://doi.org/10.1016/j.bmc.2007.04.029
  10. S.S. Feng and G. Haung, Effects of emulsifiers on the controlled release of paclitaxel(Taxol) from nanospheres of biodegradable polymers, J. Control. Release, 71, 53-69 (2001) https://doi.org/10.1016/S0168-3659(00)00364-3
  11. P. Labrie, S.P. Maddaford, J. Lacroix, C. Catalano, D.K.H. Lee, S. Rakhit and R.C. Gaudreault, In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450, Bioorg. Med. Chem., 14 7972-7987 (2006) https://doi.org/10.1016/j.bmc.2006.07.055
  12. S. Peltier, J.M. Oger, F. Lagarce, W. Couet and J.P. Benoît, Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded lipid nanocapsules, Pharm. Res., 23, 1243-1250 (2006) https://doi.org/10.1007/s11095-006-0022-2
  13. M.D. Chavanpatil, Y. Pati and J. Panyama, Susceptibility of nanoparticle encapsulated paclitaxel to p-glycoproteinmediated drug efflux, Int. J. Pharm., 320, 150-156 (2006) https://doi.org/10.1016/j.ijpharm.2006.03.045
  14. S.H. Jung, J.E. Lee, H. Seong and B.C. Shin, Preparation of the dexamethasone-incorporated lipid nanosphere: Characteristics of lipid nanosphere by varying species and ratio of lipid, J. Kor. Chem. Soc., 50, 464-470 (2006) https://doi.org/10.5012/jkcs.2006.50.6.464
  15. S.H. Jung, J.E. Lee, H. Seong and B.C. Shin, Preparation of dexamethasone-21-palmitate incorporated lipid nanosphere: Physical properties by varying components and ratio of lipid, J. Kor. Pharm. Sci., 36, 224-261 (2006) https://doi.org/10.1002/jps.3030360711
  16. H. Ohvo-Rekila, B. Ramstedt, P.L. ki and J.P. Slotte, Cholesterol interactions with phospholipids in membranes, Prog. Lipid Res., 41, 66-97 (2002) https://doi.org/10.1016/S0163-7827(01)00020-0
  17. R.L. Hong, C.J. Huang, Y.L. Teng, V.F. Pang, S.T. Chen, J.J. Liu and F.H. Chang, Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice, Clin. Cancer Res., 5, 3645-3652 (1999)
  18. E. Zimmermann and R.H. Müller, Electrolyte- and pHstabilities of aqueous solid lipid nanoparticle ($SLN^{TM}$) dispersions in artificial gastrointestinal media, Eur. J. Pharm. Biopharm., 52, 203-210 (2001) https://doi.org/10.1016/S0939-6411(01)00167-9
  19. V.M. Samsonov, N.Y. Sdobnyakov and A.N. Bazulev, Size dependence of the surface tension and the problem of Gibbs thermodynamics extension to nanosystems, Colloids and Surfaces, 239, 113-117 (2004) https://doi.org/10.1016/j.colsurfa.2004.01.016
  20. M.N. Magomedov, Dependence of the surface energy on the size and shape of a nanocrystal, Phys. Solid State, 46, 954-968 (2004) https://doi.org/10.1134/1.1744976
  21. Y. Hu, J. Xie, Y.W. Tong and C.H. Wang, Effect of PEG conformation and particle size on the cellular uptake efficiency of nanoparticles with the HepG2 cells, J. Control. Release, 118, 7-17 (2007) https://doi.org/10.1016/j.jconrel.2006.11.028