TARGETED DELIVERY OF A HEME OXYGENASE INHIBITOR WITH A LYOPHILIZED LIPOSOMAL TIN MESOPORPHYRIN FORMULATION

被引:14
作者
CANNON, JB [1 ]
MARTIN, C [1 ]
DRUMMOND, GS [1 ]
KAPPAS, A [1 ]
机构
[1] ROCKEFELLER UNIV, NEW YORK, NY 10021 USA
关键词
HEME OXYGENASE INHIBITOR; HYPERBILIRUBINEMIA; TIN MESOPORPHYRIN; LIPOSOMES; LYOPHILIZATION; TARGETED DELIVERY TO SPLEEN;
D O I
10.1023/A:1018911816814
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Tin mesoporphyrin (SnMP) is a competitive inhibitor of heme oxygenase being examined clinically for the treatment of hyperbilirubinemia. Since liposomes have been shown to target SnMP to the spleen and increase its efficacy (S. A. Landaw, G. S. Drummond, and A. Kappas, Pediatrics 84, 1091-1096, 1989), we began investigating the feasibility of the preparation and scaleup of a liposomal SnMP formulation for clinical use. SnMP liposomes were prepared by high-pressure homogenization of a suspension of SnMP and egg phosphatidylcholine (1:20, w/w) in lactose-phosphate buffer, resulting in SnMP liposomes that were less than 200 nm in diameter and had encapsulation efficiencies of up to 90% at pH 5. The SnMP liposomes could be sterile filtered and lyophilized in a 1-day cycle with retention of the encapsulation efficiency and particle size. Following injection into rats, the distribution of liposomal SnMP to spleen at 2 and 6 hr after dosing was 5-20 times higher than for aqueous SnMP. Lyophilized SnMP liposomes were also more effective than aqueous SnMP in decreasing bilirubin production in bile-cannulated rats. The results suggest the potential for producing a safe, sterile, and effective lyophilized formulation of SnMP liposomes for targeting of heme oxygenase inhibitors to the spleen.
引用
收藏
页码:715 / 721
页数:7
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