Journal of Pharmaceutical Investigation

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

DOI QR Code

Preparation of Phospholipid Nanoemulsions Loaded with Paclitaxel

파클리탁셀을 함유한 인지질 나노 에멀젼 제조

  • Seo, Dong-Hoan (College of pharmacy, Sung Kyun Kwan University) ;
  • Han, Hee-Dong (Nanobiomaterials Laboratory, Korea Research Institute of Chemical Technology) ;
  • Chi, Sang-Cheol (College of pharmacy, Sung Kyun Kwan University) ;
  • Shin, Byung-Cheol (Nanobiomaterials Laboratory, Korea Research Institute of Chemical Technology)
  • 서동환 (성균관대학교 약학대학) ;
  • 한희동 (한국화학연구원 나노생체재료연구팀) ;
  • 지상철 (성균관대학교 약학대학) ;
  • 신병철 (한국화학연구원 나노생체재료연구팀)
  • Published : 2004.04.20
Download PDF
⟨ Previous Next ⟩

Abstract

Paclitaxel is an effective antineoplastic drug for various cancers especially ovarian and breast cancer. This study is to find the optimum condition for the preparation of nanoemulsions and to improve the stability and loading amount of paclitaxel in nanoemulsions. Nanoemulsions were prepared by modified spontaneous emulsification solvent diffusion method. It was composed of phosphatidylcholine:cholesterol:1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-[Metoxy (Polyethylene glycol)-2000]:paclitaxel at a weight ratio of 5:3:1:1 and the Tween 80 as a surfactant. The particle size and the shape of nanoemulsions were measured by particle analyzer and SEM, respectively. The loading amount of paclitaxel in nanoemulsion was measured by UV-visible spectroscopy at 227 nm. The particle sizes were $80{\sim}120\;nm$ and the loading efficiency of paclitaxel was $8{\sim}39%$. The optimum conditions for the preparation of nanoemulsions were 8% w/w phospholipid, 16% w/v Tween 80 and 2% w/w paclitaxel, respectively.

Keywords

References

  1. S.S. Feng and G. Huang, Effects of emulsifiers on the controlled release of paclitaxel(Taxol$^{\circledR}$) from nanospheres of biodegradable polymers, J. Control. Release, 71, 53-69 (2001) https://doi.org/10.1016/S0168-3659(00)00364-3
  2. M.F. Shieh, I.M. Chu, CJ. Lee, P. Kan, D.M. Hau and J.J. Shieh, Liposomal delivery system for Taxol, J. Fermentation. Bioeng., 83, 87-90 (1997) https://doi.org/10.1016/S0922-338X(97)87332-1
  3. M. Schmitt-Sody, S. Strieth, S. Krasnici, B. Sauer, B. Schulze, M. Teifel, U. Michaelis, K. Naujoks and M. Dellian, Neovascular targeting therapy: paclitaxel encapsulated in cationic liposome improves antitumoral efficacy, Clin. Cancer Res., 6, 2335-2341 (2003)
  4. R. Kunstfeld, G. Wickenhauser, U. Michaelis, M. Teifel, W. Umek, K. Naujoks, K Wolff and P. Petzelbauer, Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a 'Humanizes' SCIM mouse model, J. Invest. Dermatol., 120, 476-482 (2003) https://doi.org/10.1046/j.1523-1747.2003.12057.x
  5. S.C. Kim, D.W. Kim, Y.H. Shim, J.S. Bang, H.S. Oh, S.W. Kim and M.H. Seo, In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy, J. Control. Release, 72, 191-202 (2001) https://doi.org/10.1016/S0168-3659(01)00275-9
  6. B.B. Lundberg, V. Risovic, M. Ramaswamy and K.M. Wasan, A lipophilic paclitaxel derivative incorporated in a lipid emulsion for parenteral administration, J. Control. Release, 86, 93-100 (2003) https://doi.org/10.1016/S0168-3659(02)00323-1
  7. L. He, G.L. Wang and Q. Zhang, An alternative paclitaxel microemulsion formulation: hypersensitivity evaluation and pharmacokinetic profile, Int. J. Pharm., 250, 45-50 (2003)
  8. S. Alcaro, C.A. Ventura, D. Paolino, D. Battaglia, F. Ortuso, L. Cattel, G. Puglisi and M. Fresta, Preparation, characterization, molecular modeling and in vitro activity of paclitaxel-cyclodextrin complexes, Bioorg. Med. Chem. Lett., 12, 1637-1641 (2002) https://doi.org/10.1016/S0960-894X(02)00217-2
  9. P. Kan, Z.B. Chen, C.J. Lee and I.M. Chu, Development of nonionic surfactant/phospholipid o/w emulsion as a paclitaxel delivery system, J. Control. Res., 58, 271-278 (1999) https://doi.org/10.1016/S0168-3659(98)00164-3
  10. D.G. Rodrigues, C.C. Covolan, S.T. Cora야:, R. Barboza and R.C. Maranhao, Use of a cholesterol-rich emulsion that binds to low-density lipoprotein receptors as a vesicle for paclitaxel, J. Pharma. Pharmacol., 54, 765-772 (2002) https://doi.org/10.1211/0022357021779104
  11. H. Murakami, M. Kobayashi, H. Takeuchi and Y. Kawashima, Preparation of poly(DL-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method Int. J. Pharm., 187, 143-152 (1999)
  12. L.Z. Wang, P.C. Ho, H.S. Lee, H.K Vaddi, Y.W. Chan and C.S. Yung, Quantitation of paclitaxel in macro-sample rat plasma by a sensitive reversed-phase HPLC assay, J. Pharmaceut. Biomed., 31, 283-289 (2003) https://doi.org/10.1016/S0731-7085(02)00611-8
  13. G. Theodoridis, G. Laskaris, C.F. de Jong, A.J.P Hofte and R. Verpoorte, Determination of paclitaxel and related diterpenoids in plant extracts by high-performance liquid chromatography with UV detection in high-performance liquid chromato-graphy-mass spectrometry, J. Chromatogr. A, 802, 297-305 (1998) https://doi.org/10.1016/S0021-9673(97)01174-6
  14. H.Y. Kwon, J.Y. Lee, S.W. Chio, Y.S. Jang and J.H. Kim, Preparation of PLGA nanoparticles containing estrogen by emulsification-diffusion method, Colloids and surfaces, 182, 123-130 (2001) https://doi.org/10.1016/S0927-7757(00)00825-6
  15. S.J. Park, S.H. Kim, J.R. Lee, H.B.. Lee and S.K. Hong, Preparation and characterization of biodegradable Poly( $\varepsilon$ - caprolactone) microcapsules containing erythromycin by emulsion solvent evaporation technique, Polymer(Korea), 26, 326-334 (2002)
  16. P. Kan, Z.B. Chen, R.Y. Kung, C.J. Lee and I.M. Chu, Study on the formulation of o/w emulsion as carriers for lipopholic drugs, Colloids and Surface. B. -Biointerfaces, 15, 117-125 (1999) https://doi.org/10.1016/S0927-7765(99)00048-X
  17. M. Jumaa and B.W. Muller, Parenteral emulsions stabilized with of phospholipids and PEG-660-12-hydroxy-stearate: evaluation of accelerated and long-term stability, Eur. J. Pharm. Biopharm., 54, 207-212 (2002) https://doi.org/10.1016/S0939-6411(02)00057-7
  18. K.M. Park, M.K. Lee, K.J. Hwang and C.K. Kim, Phospholipid-based microemulsions of flubiprofen by the spontaneous emulsification process, Int. J. Pharm., 183, 145-154 (1999)
  19. J.D. Ng, B. Lober, J. Witz, A.T. Dietrich D. Kern and R Giege, The crystallization of biological macromolecules from precipitates: evidence for Ostwald ripening, J. Cryst. Growth, 168, 50-62 (1996) https://doi.org/10.1016/0022-0248(96)00362-4
  20. T. Suzuki, H. Komatsu and K. Miyajima, Effects of glucose and its oligomers on the stability of freeze-dried liposomes, Bioch. Biophy. Acta, 1278, 176-182 (1996) https://doi.org/10.1016/0005-2736(95)00221-9