Preclinical evaluation of alternative pharmaceutical delivery vehicles for paclitaxel

Walter J. Loos, J. Szebeni, Albert J. Ten Tije, Jaap Verweij, Desirée M. Van Zomeren, Kyu Nung Chung, Kees Nooter, Gerrit Stoter, Alex Sparreboom

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

New solubilizers, including Sorporol 230, Sorporol 120Ex, Aceporol 345-T, Aceporol 460 and Riciporol 335, as potential new delivery vehicles for paclitaxel were investigated, since recent studies have shown that the paclitaxel delivery vehicle Cremophor EL significantly alters the pharmacokinetics of paclitaxel. Cremophor EL and Tween 80 were used as a reference. As in the case of Cremophor EL, alteration of blood distribution of paclitaxel occurred in the presence of all tested vehicles. Also, no differences in the affinity of paclitaxel for the tested solubilizers was found during equilibrium dialysis experiments. The different vehicles could be distinguished by a different rate of esterase-mediated breakdown, which was correlated with the fatty acid content of the solubilizers. The activation of the complement cascade was less pronounced for all solubilizers, except Riciporol 335, compared to Cremophor EL. The strategies presented here provide the possibility to rapidly screen future candidate delivery vehicles with optimal characteristics for use as a solubilizer in clinical formulations of paclitaxel or other poorly water-soluble drugs.

Original languageEnglish
Pages (from-to)767-775
Number of pages9
JournalAnti-Cancer Drugs
Volume13
Issue number7
DOIs
Publication statusPublished - Aug 2002

Fingerprint

Pharmaceutical Vehicles
Paclitaxel
Polysorbates
Complement Activation
Esterases
Dialysis
Fatty Acids
Pharmacokinetics
cremophor EL
Water

Keywords

  • Cremophor EL
  • Drug delivery vehicle
  • Paclitaxel
  • Solubilizer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology

Cite this

Loos, W. J., Szebeni, J., Ten Tije, A. J., Verweij, J., Van Zomeren, D. M., Chung, K. N., ... Sparreboom, A. (2002). Preclinical evaluation of alternative pharmaceutical delivery vehicles for paclitaxel. Anti-Cancer Drugs, 13(7), 767-775. https://doi.org/10.1097/00001813-200208000-00012

Preclinical evaluation of alternative pharmaceutical delivery vehicles for paclitaxel. / Loos, Walter J.; Szebeni, J.; Ten Tije, Albert J.; Verweij, Jaap; Van Zomeren, Desirée M.; Chung, Kyu Nung; Nooter, Kees; Stoter, Gerrit; Sparreboom, Alex.

In: Anti-Cancer Drugs, Vol. 13, No. 7, 08.2002, p. 767-775.

Research output: Contribution to journalArticle

Loos, WJ, Szebeni, J, Ten Tije, AJ, Verweij, J, Van Zomeren, DM, Chung, KN, Nooter, K, Stoter, G & Sparreboom, A 2002, 'Preclinical evaluation of alternative pharmaceutical delivery vehicles for paclitaxel', Anti-Cancer Drugs, vol. 13, no. 7, pp. 767-775. https://doi.org/10.1097/00001813-200208000-00012
Loos, Walter J. ; Szebeni, J. ; Ten Tije, Albert J. ; Verweij, Jaap ; Van Zomeren, Desirée M. ; Chung, Kyu Nung ; Nooter, Kees ; Stoter, Gerrit ; Sparreboom, Alex. / Preclinical evaluation of alternative pharmaceutical delivery vehicles for paclitaxel. In: Anti-Cancer Drugs. 2002 ; Vol. 13, No. 7. pp. 767-775.
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