A Novel Paclitaxel Microemulsion Containing a Reduced Amount of Cremophor EL: Pharmacokinetics, Biodistribution, and In Vivo Antitumor Efficacy and Safety

Ying Wang,Qiang Zhang,Xin Zhao,Su Chen,Shu-Fang Nie,Xin Wang,Wei-San Pan,Bing-Xiang Zhao,Xuan Zhang,Ke-Chun Wu

doi:10.1155/2011/854872

Ying Wang, Qiang Zhang + Show 8 more

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https://doi.org/10.1155/2011/854872

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Abstract

The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had similar pharmacokinetics and antitumor efficacy as the commercially available PTX injection, but a significantly reduced allergic effect due to the CrEL. The pharmacokinetics, biodistribution, in vivo antitumor activity and safety of PTX microemulsion was evaluated. The results of pharmacokinetic and distribution properties of PTX in the microemulsion were similar to those of the PTX injection. The antitumor efficacy of the PTX microemulsion in OVCRA-3 and A 549 tumor-bearing animals was similar to that of PTX injection. The PTX microemulsion did not cause haemolysis, erythrocyte agglutination or simulative reaction. The incidence and degree of allergic reactions exhibited by the PTX microemulsion group, with or without premedication, were significantly lower than those in the PTX injection group (P < .01). In conclusion, the PTX microemulsion had similar pharmacokinetics and anti-tumor efficacy to the PTX injection, but a significantly reduced allergic effect due to CrEL, indicating that the PTX microemulsion overcomes the disadvantages of the conventional PTX injection and is one way of avoiding the limitations of current injection product while providing suitable therapeutic efficacy.

Highlights

Paclitaxel (PTX) is one of the most important compounds which has recently been obtained from a natural source [1]
The average particle size of the PTX microemulsion after the concentrated solution was diluted with 5% glucose infusion was approximately 142.4 ± 1.2 nm with a polydispersity of 0.267 ± 0.07
transmission electron microscope (TEM) was used to examine the morphology of the PTX microemulsion (Figure 1(b))

Summary

Introduction

Paclitaxel (PTX) is one of the most important compounds which has recently been obtained from a natural source [1]. It is approved for the treatment of ovarian, breast, nonsmall cell lung carcinomas and AIDS-related Kaposi’s sarcoma. The currently available pharmaceutical formulation of PTX (such as Taxol, Bristol-Myers Squibb, New York, NY, USA) contains 30 mg PTX dissolved in 5 mL 50% Cremophor EL (polyethoxylated castor oil, CrEL) and 50% dehydrated ethanol (1 : 1, v/v) to enhance the solubility of PTX in water. The premedication schedule includes corticosteroids, diphenhydramine or chlorpheniramine, H2-receptor antagonists and antiemetics. CrEL has been used to administer other drugs, such as cyclosporine and teniposide, the amount of CrEL necessary to deliver the required doses of Taxol is significantly higher than that used with any other commercially available drugs [2]

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