High bioavailabilty of alpha-tocopherol loaded into poly (DL-lactic-co-glycolic acid) microspheres in apolipoprotein B knockout mice.
OBJECTIVE
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.
Yokogawa
Koichi
K
Department of Hospital Pharmacy, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Shima
Yuichiro
Y
Hashimoto
Tomoka
T
Hiyajyo
Makoto
M
Kadoyama
Kaori
K
Ishizaki
Junko
J
Nomura
Masaaki
M
Miyamoto
Ken-ichi
K
D000818:Animals; D001682:Biological Availability; D005260:Female; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008863:Microspheres; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018110:Receptors, Lipoprotein / Q000172:deficiency* / Q000235:genetics*; D014018:Tissue Distribution / Q000235:genetics; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D011108:Polymers; D018110:Receptors, Lipoprotein; C072413:apolipoprotein B receptor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D024502:alpha-Tocopherol