Abstract
Purpose. To assess the potential clinical value of α-tocopherol-loaded poly (DL-lactic-co-glycolic acid) (PLGA) microspheres, we examined the disposition kinetics of α-tocopherol after administration of the microspheres to apolipoprotein B (apo B) knockout mice as a model of abetalipoproteinemia.
Methods. PLGA microspheres containing α-tocopherol were prepared by a solvent-evaporation method. The concentration of α-tocopherol was measured by gas chromatography-mass spectrometry.
Results. The mean value of particle size of α-tocopherol-loaded PLGA microspheres was 108 μm. The loading and the trapping efficiency of α-tocopherol in PLGA microspheres were 20.8% and 86.6%, respectively. When α-tocopherol solution (25 mg/kg) was subcutaneously administered to apob (+/+) and apob (+/∖-) mice, the plasma concentrations of α-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 α-tocopherol-loaded PLGA microspheres (100 mg/kg) were subcutaneously administered, the plasma concentrations of α-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 α-tocopherol is expected to be a very useful drug delivery system in vitamin E supplementation therapy for abetalipoproteinemia.
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References
D. J. Rader and H. B. Jr Brewer. ABL (new insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease). JAMA 270:865-869 (1993).
R. E. Gregg and J. R. Wetterau. The molecular basis of ABL. Curr. Opin. Lipido. 5:81-86 (1994).
K. Ohashi, S. Ishibashi, J. Osuga, R. Tozawa, K. Harada, N. Yahagi, F. Shionoiri, Y. Iizuka, Y. Tamura, R. Nagai, D. R. Illingworth, T. Gotoda, and N. Yamada. Novel mutations in the microsomal triglyceride transfer protein gene causing ABL. J. Lipid Res. 41:1199-1204 (2000).
D. P. Muller, J. K. Lloyd, and O. H. Wolff. Vitamin E and neurological function. Lancet 1:225-228 (1983).
P. Runge, D. P. Muller, J. McAllister, D. Calver, J. K. Lloyd, and D. Taylor. Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinaemia. Br. J. Ophthalmol. 70:166-173 (1986).
K. Yokogawa, Y. Shima, T. Hashimoto, M. Hiyajyo, K. Kadoyama, J. Ishizaki, M. Nomura, and K. Miyamoto. Disposition kinetics of α-tocopherol in apolipoprotein B knockout mice. Pharm. Res. 20:368-372 (2002).
V. N. Kirilenko and G. Gregoriadis. Fat soluble vitamins in liposomes: studies on incorporation efficiency and bile salt induced vesicle disintegration. J. Drug Target. 1:361-368 (1993).
V. Bontempo, A. Baldi, F. Cheli, F. Fantuz, I. Poliis, S. Carli, and V. Dell'Orto. Kinetic behavior of three preparations of alpha-tocopherol after oral administration to postpubertal heifers. Am. J. Vet. Res. 61:589-593 (2000).
K. R. Martin, G. Loo, and M. L. Failla. Human lipoproteins as a vehicle for the delivery of beta-carotene and alpha-tocopherol to HepG2 cells. Proc. Soc. Exp. Biol. Med. 214:367-373 (1997).
H. Okada, Y. Doken, Y. Ogawa, and H. Toguchi. Preparation of three month depot injectable michrospheres of leuprorelin acetate using biodegradable polymers. Pharm. Res. 11:1143-1147 (1994).
R. Jalil and J. R. Nixon. Biodegradable poly(lactic acid) and poly(lactide-co-glycolide) microcapsules: problems associated with preparative techniques and release properties. J. Microencapsul. 7:297-325 (1990).
N. Wakiyama, K. Juni, and M. Nakano. Preparation and evaluation in vitro of polylactic acid microspheres containing local anesthetics. Chem. Pharm. Bull. 29:3363-3368 (1981).
T. Urata, K. Arimori, and H. Nakano. Modification of release rates of cyclosporin A from poly(L-lactic acid) microspheres by fatty acid esters and in-vivo evaluation of the microsperes. J. Control Release 58:133-141 (1999).
M. Nakanishi, K. Tsuchiya, K. Sakaguchi, and T. Fujita. Simultaneous determination of α-tocopherol and α-tocopheryl acetate in plasma by mass fragmentography. Yakugaku Zasshi 99:1037-1041 (1979).
K. Yamaoka, Y. Tanigawara, T. Nakagawa, and T. Uno. A pharmacokinetic analysis program (MULTI) for microcomputer. J. Pharmacobiodyn. 4:879-885 (1981).
X. Li, Y. Zhang, R. Yan, M. Zhang, M. Yuan, X. Deng, and Z. Huang. Body distribution of poly-DL-lactide-poly(ethylene glycol) microspheres with entrapped Leptospira interrogans antigens following intravenous and oral administration to guinea-pigs. J. Pharm. Pharmacol. 52:763-770 (2000).
J. C. Cox and A. R. Coulter. Adjuvants: a classification and review of their modes of action. Vaccine 15:248-256 (1997).
N. Wakiyama, K. Juni, and M. Nakano. Preparation and evaluation in vitro and in vivo of poly(lactic acid) microspheres containing dibucaine. Chem. Pharm. Bull. 30:3719-3727 (1982).
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Yokogawa, K., Shima, Y., Hashimoto, T. et al. High Bioavailability of α-Tocopherol Loaded into Poly (DL-Lactic-co-Glycolic Acid) Microspheres in Apolipoprotein B Knockout Mice. Pharm Res 20, 1846–1850 (2003). https://doi.org/10.1023/B:PHAM.0000003384.38161.ba
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DOI: https://doi.org/10.1023/B:PHAM.0000003384.38161.ba