Preparation, characterization and in vivo evaluation of 120-day poly(D,L-lactide) leuprolide microspheres

被引:86
作者
Woo, BH
Kostanski, JW
Gebrekidan, S
Dani, BA
Thanoo, BC
DeLuca, PP
机构
[1] Univ Kentucky, Coll Pharm, Fac Pharmaceut Sci, Lexington, KY 40536 USA
[2] Bristol Myers Squibb Co, Pharmaceut Res Inst, New Brunswick, NJ 08903 USA
[3] Wyeth Ayerst Labs, Cherry Hill, NJ 08002 USA
[4] Oakwood Labs, Oakwood, OH 44146 USA
关键词
leuprolide; luteinizing hormone-releasing hormone (LHRH) analogue; poly(D; L-lactide); microspheres; testosterone suppression;
D O I
10.1016/S0168-3659(01)00403-5
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A 120-day poly(D,L-lactide) (PLA) microsphere delivery system for a luteinizing hormone-releasing hormone (LHRH) analogue, leuprolide, was prepared and evaluated. Leuprolide microspheres were prepared with PLA (m.w. 11 000 Da) by a dispersion/solvent extraction-evaporation method and characterized for drug load by HPLC, particle size by laser diffractometry and surface morphology by scanning electron microscopy. In vitro peptide release and polymer degradation were studied using a modified dialysis method. Serum peptide and testosterone levels were analyzed after subcutaneous administration using a rat model. Spherical microspheres with a mean diameter of 52 mum containing 13.4% peptide released 10% of the peptide within 24 h, followed by a linear release for 150 days. Serum leuprolide levels increased immediately after administration of the microspheres to 45.6 ng/ml, but then fell to 4.3 ng/ml at 15 days and similar to2.0 ng/ml at 30 days where they remained for 120 days. The testosterone levels increased initially to 15 ng/ml and then decreased to below 0.5 ng/ml by day 4 where they remained for 120 days. In conclusion, a 120-day microsphere formulation of leuprolide was developed with excellent controlled peptide release characteristics and in vivo efficacy. (C) 2001 Elsevier Science BY. All rights reserved.
引用
收藏
页码:307 / 315
页数:9
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