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15%). The lower limit of quantification is 0.5 ng/mL in tissue homogenates (10 ng/g tissue), and the standard curve is linear up to 1000 ng/mL, with precision and accuracy 
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doi:10.1016/j.ejpb.2004.06.009 
Copyright © 2004 Elsevier B.V. All rights reserved.
Research paper
Development and characterization of a novel Cremophor® EL free liposome-based paclitaxel (LEP-ETU) formulation
J. Allen Zhang, Gopal Anyarambhatla1, Lan Ma1, Sydney Ugwu, Tong Xuan, Tommaso Sardone and Imran Ahmad
, 
Received 29 March 2004;
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Abstract
Taxol® is a marketed product for the treatment of ovarian, breast, non-small cell lung cancer and AIDS-related Kaposi's Sarcoma. It is thus far one of the most effective anticancer drugs available on the market. However, paclitaxel is only sparingly soluble in water and therefore, intravenous administration depends on the use of the non-ionic surfactant Cremophor® EL (polyethoxylated castor oil) to achieve a clinically relevant concentrated solution. Unfortunately, Cremophor® EL increases toxicity and leads to hypersensitivity reactions in certain individuals. We have developed a well characterized novel lyophilized liposome-based paclitaxel (LEP-ETU) formulation that is sterile, stable and easy-to-use. The mean particle size of the liposomes is about 150 nm before and after lyophilization, and the drug entrapment efficiency is greater than 90%. Stability data indicated that the lyophilized LEP-ETU was physically and chemically stable for at least 12 months at 2–8 and 25 °C. Moreover, the formulation can be diluted to about 0.25 mg/ml without drug precipitation or change in particle size. In vitro drug release study in phosphate-buffered saline (PBS, pH 7.4) showed that less than 6% of the entrapped paclitaxel was released after 120 h, indicating that the drug is highly stable in an entrapped form at physiologic temperature.
Keywords: Liposome-based formulation; Paclitaxel; Liposomes; Stability; Lyophilization; Taxol®; Entrapment
Article Outline
- 1. Introduction
- 2. Materials and methods
- 2.1. Solubility studies
- 2.2. Liposome preparation
- 2.3. Liposome characterization
- 2.3.1. Vesicle size measurement
- 2.3.2. Freeze-fracture electron microscopy (EM)
- 2.3.3. Negative-stain transmission electron microscopy (TEM)
- 2.4. Quantification of paclitaxel and lipids
- 2.5. Entrapment efficiency of paclitaxel
- 2.6. In vitro drug release study
- 2.7. Short-term and long-term stability studies of LEP-ETU
- 2.8. Residual moisture content determination
- 3. Results and discussion
- 3.1. Pre-formulation
- 3.2. Formulation development
- 3.3. Characterization of pre-lyophilized and reconstituted LEP-ETU
- 3.4. In vitro dialysis study
- 3.5. Entrapment efficiency of paclitaxel
- 3.6. Short-term and long-term stabilities
- References
