High bioavailabilty of alpha-tocopherol loaded into poly (DL-lactic-co-glycolic acid) microspheres in apolipoprotein B knockout mice.

Abstract

PURPOSE:

To assess the potential clinical value of alpha-tocopherol-loaded poly (DL-lactic-co-glycolic acid) (PLGA) microspheres, we examined the disposition kinetics of alpha-tocopherol after administration of the microspheres to apolipoprotein B (apo B) knockout mice as a model of abetalipoproteinemia.

METHODS:

PLGA microspheres containing alpha-tocopherol were prepared by a solvent-evaporation method. The concentration of alpha-tocopherol was measured by gas chromatography-mass spectrometry.

RESULTS:

The mean value of particle size of alpha-tocopherol-loaded PLGA microspheres was 108 microm. The loading and the trapping efficiency of alpha-tocopherol in PLGA microspheres were 20.8% and 86.6%, respectively. When alpha-tocopherol solution (25 mg/kg) was subcutaneously administered to apob (+/+) and apob (+/-) mice, the plasma concentrations of alpha-tocopherol reached a peak at 6 h and decreased to the endogenous level within 4 days in both types of mice. However, the area under the plasma concentration-time curve (AUC) of apob (+/-) mice was significantly smaller than that in the case of apob (+/+) mice. When alpha-tocopherol-loaded PLGA microspheres (100 mg/kg) were subcutaneously administered, the plasma concentrations of alpha-tocopherol increased slowly and remained about 2-fold higher than the endogenous level at 5 to 10 days after administration in both types of mice, and there was no significant difference between the AUC values.

CONCLUSIONS:

The PLGA microsphere preparation of alpha-tocopherol is expected to be a very useful drug delivery system in vitamin E supplementation therapy for abetalipoproteinemia.

• Authors: Koichi Yokogawa, Yuichiro Shima, Tomoka Hashimoto, Makoto Hiyajyo, Kaori Kadoyama, Junko Ishizaki, Masaaki Nomura, Ken-ichi Miyamoto
• Journal: Pharmaceutical research (Pharm Res) Vol. 20 Issue 11 Pg. 1846-50 (Nov 2003) ISSN: 0724-8741 [Print] United States
• PMID: 14661931 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Polymers
• Receptors, Lipoprotein
• apolipoprotein B receptor
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• alpha-Tocopherol

Topics

• Animals
• Biological Availability
• Female
• Injections, Subcutaneous
• Lactic Acid (administration & dosage, pharmacokinetics)
• Liver (metabolism)
• Male
• Mice
• Mice, Knockout
• Microspheres
• Polyglycolic Acid (administration & dosage, pharmacokinetics)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polymers (administration & dosage, pharmacokinetics)
• Receptors, Lipoprotein (deficiency, genetics)
• Tissue Distribution (genetics)
• alpha-Tocopherol (administration & dosage, blood, pharmacokinetics)