聚乳酸-羟基乙酸共聚物吗啡微球的制备及其镇痛作用

背景：药物微球因其对特定器官和组织的靶向性及微粒中药物释放的缓释性而成为一种新的给药系统。国内外学者对局麻药缓释给药系统进行了一系列研究,但麻醉性镇痛药的微球制剂未见报道。 目的：制备以聚乳酸-羟基乙酸共聚物为载体的吗啡生物可降解缓释微球制剂,并检测其镇痛作用。 方法：采用溶剂挥发法制备吗啡聚乳酸-羟基乙酸共聚物微球,并计算其载药量及包封率。将雄性健康SD大鼠以数字表法随机分为3组：空白对照组(皮下注射生理盐水),阳性对照组(皮下注射盐酸吗啡注射剂)和吗啡微球组(皮下注射吗啡聚乳酸-羟基乙酸共聚物微球),利用CO2激光为热刺激进行痛阈测定。 结果与结论：制成的吗啡聚乳酸-羟基乙酸共聚物微球为白色粉末,载药量为11.86%,药物包封产率为33%,微球可较明显延长吗啡作用时间至6 h以上。结果说明吗啡聚乳酸-羟基乙酸共聚物微球明显地延长了吗啡释放时间,缓释性好,但未达到预期的理想时间,仍然需要进行改进。

Preparation of polylactic-co-glycolic acid morphine microspheres and their analgesia effect

BACKGROUND: Drug microspheres have become a new drug delivery system because of the targeting on specific organs and tissues, as well as slow-release of drugs in particles. Scholars have conducted a series of studies on local anesthetic drug slow-release delivery system, but preparation of narcotic analgesic microspheres is rarely reported. OBJECTIVE: To prepare biodegradable slow-release microspheres based on polylactic-co-glycolic acid (PLGA) and morphine, to study the analgesia effect. METHODS: Morphine-PLGA microspheres were prepared by using emulsify-solvent evaporation method, their entrapment efficiency and drug loading content were determined. Healthy male SD rats were divided into 3 groups randomly: blank control group (hypodermic injection of physiological saline), positive control group (hypodermic injection of morphine), microsphere group (hypodermic injection of morphine-PLGA microspheres). The pain threshold was detected using CO2 laser as thermal stimulus. RESULTS AND CONCLUSION: The morphine-PLGA microspheres were white powders. The entrapment efficiency and drug loading were 33% and 11.86%, respectively. The morphine-PLGA microspheres could prolong the time of analgesia to above 6 hours. Results demonstrated that the morphine-PLGA microspheres play a remarked prolonging role in release time of morphine, and result in a good slow-release, but the time is not enough for the expected time, so the method to prepare microspheres should be further modified.