OBJECTIVE To develop an enzyme linked immunosorbent assay(ELISA) method for the content determination of intereron α-2b PLGA microspheres in the serum of rats and study the pharmacokinetics and bioavailability of in rats after subcutaneous administration.METHODS Human IFNα ELISA kit was used for the content determination.The pharmacokinetic compartment model were fit by 3P87 pharmacokinetic program.RESULTS he calibration curve was linear over the range of 14-875 ng·L-1 with the correlation coefficients of 0.994 2 and the average of recovery was 98.09%.The within-plate and between-plates RSD values were 1.06%-7.54% and 1.34%-10.35%,respectively.Pharmacokinetic parameters of were as follows:tmax4 h,ρmax5.490×103 ng·L-1,MRT 2.486 d for IFNα-2b PLGA microspheres,and tmax 1.5 h,ρmax 2.532×104 ng·L-1,MRT 0.095 6 d for IFNα-2b solution.Pharmacokinetics data of both formulations consistent with one compartment model.CONCLUSION The ELISA method was proved to be sensitive and well reproducible and can be used successfully for the pharmacokinetics study of the IFNα-2b PLGA microspheres.Subcutaneous administration of IFNα-2b PLGA microspheres showed significant prolonged drug release and increasd bioavailability of IFNα-2b.
LU Lei;LU Ying;ZOU Ho;ZHONG Yn-qing.
Pharmacokinetics Study of Intereron α-2b PLGA Microspheres in Rats by ELISA [J]. Chinese Pharmaceutical Journal, 2008, 43(23): 1811-1814
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参考文献
[1] WANG Y S，YOUNGSTER S，GRACE M. Structural and biolog- ical characterization of pegylated recombinant interferon alpha-2b and its therapeutic implications [J] . Adv Drug Deliv Rev，2002，54(4)：547-570.
[2] YANG L，YANG W Z，BI D，et al. A novel method to prepare highly encapsulated interferon-α-2b containing liposomes for intramuscular sustained release[J] . Eur J Pharm Biopharm，2006，64：9-15.
[3] QIU J，WEI X H，GENG F，et al. Multivesicular liposome formulations for the sustained delivery of interferon α-2b [J] . Acta Pharmacol Sin，2005，26 (11)： 1395-1401.
[4] SANCHEZ A，TOBIO M，GONZALEZ L，et al. Biodegradable micro- and nanoparticles as long-term delivery vehicles for interferon-alpha [J] . Eur J Pharm Sci，2003，18：221-229.
[5] WU C，YIN D F，LU Y，et al. Formulation and preparation method of long-acting interferon α-2b loaded injectable microspheres[J] . Acad J Second Mil Med Univ(第二军医大学学报)，2006，27(1)：76-80.
[6] FAN L，LU Y，WU C，et al. Preparation and influence factors of interferon-α-2b complex-PLGA microspheres[J] . Chin J Pharm(中国医药工业杂志)，2006，37(10)：674-678.
[7] ZHENG C H，YU H Y，GAO J Q，et al. Hydrophilic biod- egradable microspheres of interferon-alpha and its pharmacokinetics in mice[J] . J Biomed Mater Res B Appl Biomater，2008 ，85(1)：225-230.
[8] YAO W B，LIN B R，SHEN Z L，et al. Study on the pharm- acokinetic of PEG-IFN α-2b in vivo[J] .J China Pharm Univ (中国药科大学学报) ，2001，32(6)：457-461.
[9] JO Y W，YOUN Y S，LEE S H， et al. Long-acting interferon-alpha 2a modified with a trimer-structured polyethylene glycol： Preparation，in vitro bioactivity，in vivo stability and pharmacokinetics[J] .Int J Pharm，2006，309(1-2)：87-93.
[10] LU B，FENG J F，YANG X C. Human Recombinant interferon-α-2a polybutylcyanoacrylate sustained release lyophilized nanospheres for liver-targeting[J] . J Sichuan Univ (Med Sci Edi）[四川大学学报（医学版）] ，2004，35 (1) ：1-4.
