• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.160-160
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• 2002

Previously, we reported a novel polymeric micellar solubilizer, Aceporol 330, that showed relatively low toxic effects when it was compared with that of Cremophor EL which is currently being used for paclitaxel. In this study, we have developed a new micellar solubilizer, Aceporol 460, that has 3-4 times higher lading capacity for paclitaxel than Aceporol 330.(omitted)

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.160-160
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• 2002

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.117-117
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• 2002

• Journal of Pharmaceutical Investigation
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• v.37 no.4
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• pp.229-235
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• 2007

Multi-layered granules were prepared by a fluidized-bed coater and uniformed granules were obtained with a size range between $950{\sim}1000{\mu}m$ in diameter. The granule system was composed of three layers, i.e. seed layer with sugar sphere bead and a water-swellable polymer, middle layer with a drug, solubilizer and polymer, and the top layer of porous membrane with a polymeric binder. The aim of this work is to find out the dependence of a drug dissolution rate on the amount of a water-soluble binder and a solubilizer in the granule system. The results showed that the higher amount of hydrophilic binder in the porous membrane, gave the bigger pore size and porosity and made faster dissolution rate and also the higher amount of solubilizer in drug layer enhanced the dissolution rate of drug.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.172-172
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• 2002

Previously, we reported a novel polymeric micellar solubilizer, Aceporol 330, that showed relatively low toxic effects when it was compared with that of Cremophor EL which is currently being used for paclitaxel. In this study, we have developed a new micellar solubilizer, Aceporol 460, that has 3-4 times higher loding capacity for paclitaxel than Aceporol 330. The single-dose and the repeated-dose toxicity of Aceporol 460 were evaluated in ICR mice. For single dose toxicity test, male and female mice were randomly assigned to one of five study groups to receive, and injected intravenously with dosages of 0, 3, 4mL Cremophor EL/kgbody weight, and 3, 4mL Aceporol 460/kg body weight, respectively. In both male and female mice, LD50 for Aceporol 460 can not he determined even at the maximal administrable dosage, 4mL/kg due to the high viscosity of chemical and there was no significant change in body weight, hematological and serum biochemical analysis, organ weight, and histopathological examination compared with that of Cremophor EL. For the repeated dose toxicity test, male and female mice were given the dosage of 0, 1.6mL Cremophor EL/kgbody weight/day, and 1.6mL Aceporol 460/kg body weight/day for 2 weeks. Results of repeated dose toxicity tests for 2 weeks suggested that Aceporol 460 treated group show no significant toxicological findings with body weight, hematological and serum biochemical analysis, organ weight, urinalysis, and ophthalmoscopic and histopathological examination compared with that of Cremophor EL. These results indicate that Aceporol 460 have higher paclitaxeL-loading capacity than Aceporol 330 and less toxic effects than Cremophor EL in male and female mice.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.61-68
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• 2008

In order to develop an improved paclitaxel formulation vehicle, a micelle forming solubilizer, Aceporol 330 was synthesized. It was previously reported that Aceporol 330 provided the linearity of paclitaxel plasma pharmacokinetics. In this study, the single dose toxicity test and 2-week repeated dose toxicity test of Aceporol 330 was performed in beagle dogs after intravenous administration. Single dose and 2-week repeated dose toxicity test of Aceporol 330 showed fever/generalized erythema, severe vomiting, and diarrhea in beagle dogs. However, those toxicities were less severe than those of Cremophor EL. Blood chemistry analysis of 2-week repeatedly treated beagle dogs with Aceporol 330 showed significant elevation of total cholesterol (TCHO) and triglyceride (TG) compared to that of control group. Cremophor EL also significantly increased total cholesterol (TCHO) and triglyceride (TG) as much as Aceporol 330. Results from this study indicated that Aceporol 330 was less toxic than Cremophor EL. Based on the pharmacokinetic advantages and the low toxicity of Aceporol 330 in single dose and 2-week repeated dose toxicity test, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.40-45
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• 2008

The objective of this study was to investigate the single dose and 2-week repeated dose toxicity of Aceporol 330 in ICR mice following single intravenous administration and to compare its toxicity with a commercially available solubilizer of paclitaxel, Cremophor EL. In single dose toxicity test, $LD_{50}$ of Aceporol 330 in mice was estimated to be greater than maximum applicable dose, 4 ml/kg. However, $LD_{50}$ of Cremophor EL in male mice was determined to be 4 ml/kg. Maximum tolerated dose (MTD) of males and females in Aceporol 330-treated group and MTD of females in Cremophor EL-treated group were 3 ml/kg. MTD of males in Cremophor EL-treated group was less than 3 ml/kg. Characteristic toxic symptoms, and hematological and blood chemical changes were not observed after single dose and repeated dose of Aceporol 330 or Cremophor EL. No histopathological abnormalities were found in organs of all animal groups. Based on the linear pharmacokinetic property of paclitaxel and the higher $LD_{50}$ in mice, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.117-117
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• 2002

Paclitaxel isolated from the pacific yew tree, Taxus brevifolia, is microtuble-stabilizing agent that has a promising anticancer activity against a wide variety of tumors such as ovarian, breast and lung cancers. Because of its poor water solubility, paclitaxel is currently formulated in a mixture of polyoxyethyleneglycerol triricinoleate 35 (Cremophor EL) and dehydrated ethanol USP (1:1 v/v).(omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.174-174
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• 2001

Paclitaxel is currently administered i.v. as a slow infusion of a solution of the drug in an ethanol: cremophor EL: saline admixture. However, poor solubilization and toxicity are associated with this drug therapy. We have tried to develop a new surfactant for paclitaxel to improve efficacy and reduce toxicity of solubilizer.(omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.413.2-413.2
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• 2002

Paclitaxel is an antitumor agent with poor water solubility and its pharmacokinetics are nonlinear. Cremophor EL. a surfactant used in the formulation of paclitaxel. may cause adverse effects. New solubilizer(Aceporol 460) was developed to reduce side effects of Cremophor EL and to increase the effect of drug as surfactant used in the intravenous micelle formulation of anticancer drug paclitaxel. We studied easy, rapid quantitative determination of Aceporol 460 in mouse plasma samples. which was achieved by complexation of the compound with the Coomassie brilliant blue G-250 dye in protein-free extracts. (omitted)