He G A, Hou H M, Liu X J
National Pharmaceutical Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
Acta Pharmacol Sin. 2001 Jun;22(6):530-3.
To study in vitro release and in vivo effect of four different types of sustained-release naltrexone microspheres on morphine analgesia.
Release of naltrexone from four types of biodegradable microspheres was investigated by HPLC. Their antagonist effects on morphine analgesia were observed using mouse hot-plate procedure.
Poly latide-co-glycolide (PLGA) composition had a remarkable effect on naltrexone release from microspheres and its antagonism towards morphine analgesia. Two formulations of PLGA 50:50 formulation released more than 80 % of total naltrexone and lost their antagonism by 8 d. The PLGA 75:25 formulation with 20 % and 30 % drug loadings did not release 95 % of total drug and lose antagonism until 40 d and 30 d, respectively. Increasing the drug loading enhanced naltrexone release from microspheres and seemed to shorten the analgesic antagonistic effect of naltrexone.
Antagonism by naltrexone microspheres towards morphine analgesia correlates well with the drug release in vitro.
研究四种不同类型的纳曲酮缓释微球的体外释放情况及对吗啡镇痛的体内作用。
采用高效液相色谱法研究四种可生物降解微球中纳曲酮的释放情况。利用小鼠热板法观察它们对吗啡镇痛的拮抗作用。
聚丙交酯-乙交酯（PLGA）组成对纳曲酮从微球中的释放及其对吗啡镇痛的拮抗作用有显著影响。两种PLGA 50:50配方释放了超过80%的总纳曲酮，且在8天时失去了拮抗作用。载药量为20%和30%的PLGA 75:25配方分别在40天和30天时才释放95%的总药物并失去拮抗作用。增加载药量可增强纳曲酮从微球中的释放，且似乎缩短了纳曲酮的镇痛拮抗作用。
纳曲酮微球对吗啡镇痛的拮抗作用与体外药物释放密切相关。
