Pharmaceutical Research

, Volume 20, Issue 11, pp 1864–1872 | Cite as

PLGA/TPGS Nanoparticles for Controlled Release of Paclitaxel: Effects of the Emulsifier and Drug Loading Ratio

  • Li Mu
  • Si-Shen Feng


Purpose. We successfully manufactured nanoparticles of biodegradable polymers for controlled release of paclitaxel. TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate) could be a novel material to make nanoparticles of high drug encapsulation efficiency (EE) and desired physicochemical and pharmaceutical properties of the drug loaded nanoparticles. Among various controlling parameters in the process, the present work is to elucidate the effects of the surfactant stabilizer and the drug loading ratio.

Methods. Paclitaxel loaded PLGA nanoparticles were formulated at various drug-loading ratios by a modified single emulsion solvent extraction/evaporation technique. TPGS was introduced either as the emulsifier or as a matrix material component by using different technique. Polyvinyl alcohol (PVA) was also used for a comparison. The nanoparticles of various recipes were characterized by various state-of-the-art instrument technology for their properties.

Results. The EE and the in vitro release behavior were found significantly influenced by the drug loading ratio and the surfactant stabilizer encountered. TPGS involved nanoparticles can have high EE and other favorable properties.

Conclusions. TPGS could be a novel and effective emulsifier, which can result in high EE and desired properties of paclitaxel-loaded polymeric nanoparticles.

anti-cancer agent biodegradable polymer drug delivery emulsifier D-α-tocopheryl polyethylene glycol 1000 succinate taxol 


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  1. 1.
    K. S. Soppimath, T. M. Aminabhavi, A. R. Kulkarni and W. E. Rudzinski, Biodegradable polymeric nanoparticles as drug delivery devices, J. Control Rel. 70:1-20 (2001).Google Scholar
  2. 2.
    S. M. Moghimi, A. C. Hunter, and J. C. Murray. Long-circulating and target specific nanoparticles: theory to practice. Pharmacol. Rev. 53:283-318 (2001).Google Scholar
  3. 3.
    R. Langer. Biomaterials in drug delivery and tissue engineering: one laboratory's experience. Acc. Chem. Res. 33 (2):94-101 (2000).Google Scholar
  4. 4.
    C. X. Songa, V. Labhasetwara, H. Murphya, X. Qua, W. R. Humphreyb, R. J. Shebuskib and R. J. Levy, Formulation and characterization of biodegradable nanoparticles for intravascular local drug delivery, J. Control Rel. 43:197-212 (1997).Google Scholar
  5. 5.
    V. Labhasetwar. Nanoparticles for drug delivery. Pharm. News. 4:28-31 (1997).Google Scholar
  6. 6.
    J. Couzin. Cancer Research: nanoparticles cut tumors. Science 296:2314-2315 (2002).Google Scholar
  7. 7.
    J. D. Hood, M. Bednarski, R. Frausto, S. Guccione, R. A. Reisfeld, R. Xiang, and D. A. Cheresh. Tumor Regression by Targeted Gene Delivery to the Neovasculature. Science 296:2404-2407 (2002).Google Scholar
  8. 8.
    V. Labhasetwar, C. Song, and R. J. Levy. Nanoparticle drug delivery system for restenosis. Adv. Drug Delivery Rev. 24:63-85 (1997).Google Scholar
  9. 9.
    R. H. Muller. (ed.), Colloidal Carriers for Controlled Drug Delivery and Targeting, CRC Press, Boca Raton, Florida. 1991, pp. 1-16.Google Scholar
  10. 10.
    P. D. Scholes, A. G. A. Coombes, L. Illum, et al. The preparation of sub-200 nm poly (lactide-co-glycolide) microspheres for site-specific drug delivery. J. Control Rel. 25:145-153 (1993).Google Scholar
  11. 11.
    M.F. Zambaux, F. Bonneaux, R. Gref et al. Influence of experimental parameters on the characteristics of poly (lactic acid) nanoparticles prepared by a double emulsion method. J. Control. Rel. 50:31-40 (1998).Google Scholar
  12. 12.
    A. Carrio, G. Schwach, J. Coudane, and M. Vert. Preparation and degradation of surfactant-free PLGA microspheres. J. Control Rel. 37:113-121 (1991).Google Scholar
  13. 13.
    S. C. Lee, J. T. Oh, M. H. Jang, and S. Chung. Quantitative analysis of polyvinyl alcohol on the surface of poly(D,L-lactide-co-glycolide) microparticles prepared by solvent evaporation method: effect of particle size and PVA concentration. J. Control Rel. 59:123-132 (1999).Google Scholar
  14. 14.
    D. T. Birnbaum, J. D. Kosmala, and L. Brannon-Peppas. Optimization of preparation techniques for poly(lactic acid-co-glycolide acid) nanoparticles. J. Nanoparticle Res. 2:173-181 (2000).Google Scholar
  15. 15.
    D. Quintanar-Guerrero, H. Fessi, E. Allemann, and E. Doelker. Influence of stabilizing agents and preparative variables on the formation of poly(D,L-lactic acid) nanoparticles by an emulsification-diffusion technique. Int. J. Pharmaceutics 143:133-141 (1996).Google Scholar
  16. 16.
    M. F. Zambaux, F. Bonneaux, R. Gref, P. Maincent, E. Dellacherie, M. J. Alonso, P. Labrude, and C. Vigneron. Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method. J. Control Rel. 50:31-40 (1998).Google Scholar
  17. 17.
    R. Gref, V. Babak, P. Bouillot, I. Lukina, M. Bodorev, and E. Dellacherie. Interfacial and emulsion stabilizing properties of amphiphilic water-soluble poly(ethylene glycol)-poly(lactic acid) copolymers for the fabrication of biocompatible nanoparticles. Colloids and Surfaces. A Physicochemical and Engineering Aspects. 143:413-420 (1998).Google Scholar
  18. 18.
    S. K. Sahoo, J. Panyam, S. Prabha, and V. Labhasetwar. Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. J. Controlled Release 82 (1):105-114 (2002).Google Scholar
  19. 19.
    A. K. Singla, G. Alka, and A. Deepika. Paclitaxel and its formulations. Int. J. Pharmaceutics 235:179-192 (2002).Google Scholar
  20. 20.
    E. Tatou, C. Mossiat, V. Maupoil, F. Gabrielle, M. David, and L. Rochette. Effects of cyclosporin and cremophor on working rat heart and incidence of myocardial lipid peroxidation. Pharmacol. 52:1-7 (1996).Google Scholar
  21. 21.
    R. T. Dorr. Pharmacology and toxicology of Cremophor EL diluent. Ann. Pharmacother. 28:S11-S14 (1994).Google Scholar
  22. 22.
    M. L. Fjallskog, L. Frii, and J. Bergh. Is cremophor, solvent for paclitaxel, cytotoxic? Lancet 342:873(1993).Google Scholar
  23. 23.
    L. Mu and S. S. Feng. A novel controlled release formulation for anticancer drug paclitaxel (Taxol\R): PLGA nanoparticles containing vitamin E TPGS. J. Control. Rel. 86:33-48 (2003).Google Scholar
  24. 24.
    Y. N. Konan, R. Gurny, and E. Allemann. Preparation and characterization of sterile and freeze-dried sub-200 nm nanoparticles. Int. J. Pharmaceutics 233:239-252 (2002).Google Scholar
  25. 25.
    H. Murakami, Y. Kawashima, T. Niwa, T. Hino, H. Takeuchi, and M. Kobayashi. Influence of the degrees of hydrolyzation and polymerization of poly(vinylalcohol) on the preparation and properties of poly(DL-lactide-co-glycolide) nanoparticle. Int. J. Pharmaceutics 149:43-49 (1997).Google Scholar
  26. 26.
    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. Pharmaceutics 187:143-152 (1999).Google Scholar
  27. 27.
    C. Dubernet. Thermoanalysis of microspheres. Thermochimica Acta 248:259-269 (1995).Google Scholar
  28. 28.
    P. D. Scholes, A. G. A. Coombes, L. Illum, S. S. Davis, J. F. Watts, C. Ustariz, M. Vert, and M. C. Davies. Detection and determination of surface levels of poloxamer and PVA surfactant on biodegradable nanospheres using SSIMS and XPS. J. Control Rel. 59:261-278 (1999).Google Scholar
  29. 29.
    D. Briggs and M. P. Seah. (eds), Practical Surface Analysis by Auger and X-ray Photoelectron Spectroscopy, John Wiley, Chi-chester, 1990.Google Scholar
  30. 30.
    T. Gorner, R. Gref, D. Michenot, F. Sommer, M. N. Tran, and E. Dellacherie. Lidocaine-loaded biodegradable nanospheres. I. Optimization of the drug incorporation into the polymer matrix. J. Control. Rel. 57:259-268 (1999).Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Li Mu
    • 1
  • Si-Shen Feng
    • 1
    • 2
  1. 1.Division of BioengineeringThe National University of SingaporeSingapore
  2. 2.Department of Chemical and Environmental EngineeringThe National University of SingaporeSingapore

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