[Experimental study for thrombocytopenic purpura therapy by targeting macrophages in liver and spleen].
The study purpose was to explore whether dichloromethylene diphosphonate (Cl(2)MDP)-loaded gelatin particles can induce the depletion of macrophage in reticuloendothelial system of liver and spleen or can depress the immunity of macrophage in SD rat models of immune thrombocytopenic purpura (ITP) to treat the ITP rats. New Zealand rabbits were immunized with platelets of SD rats to prepare rabbit anti-rat platelet serum, and the serum was intravenously injected into SD rats to produce the ITP model. In experimental ITP models, 150 microl of anti-platelet serum was intravenously injected into SD rats per 24 hours. The platelet counts maintained pathological level and were persistently less than 50 x 10(9)/L in the models during experiment process. The MTT test of macrophage RAW264.7 was carried out by means of Cl(2)MDP-loaded gelatin particles in vitro. After intravenous injection of a group dose of Cl(2)MDP-gelatin particles, the platelet counts of the rats were measured at the time of 4 hours, 24 hours, 48 hours, 72 hours and 96 hours, respectively, and bleeding times were detected in 24 hours. The results showed that Cl(2)MDP-loaded gelatin particles increased the platelet counts of ITP models to mean of 180 x 10(9)/L, a physiological level in 24 hours after injection, and kept this platelet level through whole process of 120 hours. Furthermore, rats pre-treated with Cl(2)MDP-loaded gelatin particles avoided the decrease of platelet counts significantly when they were injected anti-platelet serum. It is concluded that Cl(2)MDP-loaded gelatin particles restrain multiplication of macrophage RAW264.7, and promptly, effectively restore platelet counts of ITP models to physiological level in a dose dependent manner. So, the targeting therapy of drug-loaded gelatin particles offers a new idea and approach to treat ITP, and this strategy is worthy of further studies.
Tan
Zhong-Hua
ZH
Department of Nuclear Medicine, Ruijin Hospital, The Shanghai Jiaotong University, Shanghai 200025, China. zhhtan@126.com
Li
Pei-Yong
PY
Zhu
Yi-Hua
YH
Ji
Xiao-Wen
XW
Wu
Zhen-Yu
ZY
D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005780:Gelatin / Q000008:administration & dosage*; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D010316:Particle Size; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000628:therapy*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D004337:Drug Carriers; D004002:Clodronic Acid; D005780:Gelatin