Preclinical evaluation of alternative pharmaceutical delivery vehicles for paclitaxel.
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.
Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, 3008 AE Rotterdam, The Netherlands. loos@pcnh.azr.nl
Walter J
WJ
Loos
Janos
J
Szebeni
Albert J
AJ
ten Tije
Jaap
J
Verweij
Desirée M
DM
van Zomeren
Kyu-nung
KN
Chung
Kees
K
Nooter
Gerrit
G
Stoter
Alex
A
Sparreboom
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D017239:Paclitaxel / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D012015:Reference Standards; D012995:Solubility
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles; D017239:Paclitaxel