STABILITY OF ATRIOPEPTIN-III IN POLY(D,L-LACTIDE-CO-GLYCOLIDE) MICROSPHERES

被引:55
作者
JOHNSON, RE
LANASKI, LA
GUPTA, V
GRIFFIN, MJ
GAUD, HT
NEEDHAM, TE
ZIA, H
机构
[1] G.D. Searle and Co., Skokie, IL
[2] College of Pharmacy, University of Rhode Island, Kingston, RI
关键词
CONTROLLED RELEASE; PEPTIDE; POLYLACTIDE-CO-GLYCOLIDE; ATRIOPEPTIN-III; MICROSPHERE;
D O I
10.1016/0168-3659(91)90131-V
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The stability of atriopeptin III (APIII) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) microspheres has been investigated and compared to the stability of APIII alone. When the microspheres are shaken in Tris-buffered Ringer's (pH 7.4) at 40-degrees-C, the APIII inside of the microspheres is completely degraded in 5 days. Though APIII is stable in microspheres that are stored desiccated at -20-degrees-C, when the microspheres are stored in 95% relative humidity at 40-degrees-C there is 20% degradation of APIII in 8 days. Concentrated APIII, on the other hand, shows no degradation after 2 weeks at 40-degrees-C and dilute APIII in water shows no loss after 1 month at 40-degrees-C. In Tris-buffered Ringer's (pH 7.4) at 40-degrees-C, however, dilute APIII degrades with a half life of 8.7 days unshaken or 2.4 days when shaken. The pattern of degradation peaks seen during HPLC analysis of samples degraded in the presence of PLGA is different than that seen when APIII alone degrades in buffer solution. These experiments indicate that PLGA may not be an appropriate polymer for use with some peptides and proteins.
引用
收藏
页码:61 / 67
页数:7
相关论文
共 20 条
  • [1] Beck, Pope, Flowers, Cowsar, Tice, Lewis, Dunn, Moore, Gilley, Poly(dl-lactide-co-glycolide)/norethisterone microcapsules: an injectable degradable contraceptive, Biol. Reprod., 28, pp. 186-195, (1983)
  • [2] Waykiyama, Juni, Nakano, Preparation and evaluation in vitro and in vivo of polylactic acid microspheres containing dibucaine, Chem. Pharm. Bull., 30, pp. 3719-3727, (1982)
  • [3] Mason, Thies, Cicero, In vivo and in vitro evaluation of a microencapsulated narcotic antagonist, J. Pharm. Sci., 65, pp. 847-850, (1976)
  • [4] Hora, Rana, Nunberg, Tice, Gilley, Hudson, Release of human serum al-bumin from poly(lactide-co-glycolide) microspheres, Pharm. Res., 7, pp. 1190-1194, (1990)
  • [5] Sanders, McRae, Vitale, Kell, Controlled delivery of an LHRH analogue from biode-gradable injectable microspheres, Journal of Controlled Release, 2, pp. 185-187, (1985)
  • [6] Okada, Heya, Igari, Ogawa, Toguchi, Shimamoto, One-month release injectable microspheres of leuprolide acetale inhibit steroidogenesis and genital organ growth in rats, Int. J. Pharmaceutics, 54, pp. 231-239, (1989)
  • [7] Kwong, Chov, Sun, Sefton, Goosen, In vitro and in vivo release of insulin from poly(lactic acid) microbeads and pellets, J. Controlled Release, 4, pp. 47-62, (1986)
  • [8] Csernus, Szenda, Schally, Release of peptides from sustained delivery systems (microcapsules and microparticles) in vivo: a histological and immunohistochemical study, Int. J. Peptide Protein Res., 35, pp. 557-565, (1990)
  • [9] Maulding, Prolonged delivery of peptides by microcapsules, J. Controlled Release, 6, pp. 167-176, (1987)
  • [10] Lin, Ho, Chiou, Insulin controlled-release microcapsules to prolong the hypoglycemic effect in diabetic rats, Biomat. Art. Cells Art. Org., 16, pp. 815-828, (1988)