目的:观察葡聚糖接枝聚乳酸载吗啡缓释纳米粒胶束(MP/DEX-PLA)对急性疼痛大鼠的镇痛效应。方法:SD雄性大鼠40只,随机均分为4组,A组(空白对照组),B组(空白纳米胶束对照组),C组(普通吗啡组),D组(载吗啡纳米胶束组)。制备可生物降解的载吗...目的:观察葡聚糖接枝聚乳酸载吗啡缓释纳米粒胶束(MP/DEX-PLA)对急性疼痛大鼠的镇痛效应。方法:SD雄性大鼠40只,随机均分为4组,A组(空白对照组),B组(空白纳米胶束对照组),C组(普通吗啡组),D组(载吗啡纳米胶束组)。制备可生物降解的载吗啡葡聚糖接枝聚乳酸共聚物,皮下用药后测定急性疼痛大鼠的累计疼痛评分(CPS)和痛阈,评价药物的镇痛效果,观察其副作用。结果:MP/DEX-PLA纳米胶束呈球形,平均载药量为20.94%,平均包封率为36.27%。建模手术后,各组大鼠痛阈明显降低(P<0.05);给药后,C组和D组CPS明显低于B组,痛阈明显升高(P<0.05);C组和D组分别于给药后30 m in和2h时达到最大镇痛效应,C组镇痛持续时间明显短于D组(P<0.05),C组和D组痛阈最高值和CPS无明显差异(P>0.05),C组不良反应发生率显著高于D组(P<0.05)。结论:皮下单次给予MP/DEX-PLA可通过吗啡缓慢释放发挥持续镇痛作用,副作用小于普通吗啡。展开更多
Our previous studies have reported the presence of "chain delivery" effects of protein adsorption onto ion exchangers with polymer-grafted ion-exchange groups, such as dextran-grafted and poly(ethylenimine)-...Our previous studies have reported the presence of "chain delivery" effects of protein adsorption onto ion exchangers with polymer-grafted ion-exchange groups, such as dextran-grafted and poly(ethylenimine)-modified Sepharose gels. However, it is unclear if the "chain delivery" occurs on affinity adsorption with specific interactions. This work is designed to address this issue. A dextran-grafted Sepharose gel was prepared, and then the matrix was modified using diethylaminoethyl, a typical ion-exchange group, or octapeptide(FYCHWQDE), an affinity ligand for human immunoglobulin G(h Ig G) to prepare ion-exchange or affinity adsorbents, respectively.Results of h Ig G adsorption showed that the uptake rate represented by the effective diffusivity of h Ig G onto the dextran-grafted ion exchangers was obviously enhanced by the dextran grafting, indicating the presence of"chain delivery" of the bound proteins on the charged groups on the dextran chains. By contrast, the effective diffusivity of h Ig G changed little as ligand density increased on the dextran-grafted FYCHWQDE adsorbents.Their adsorption capacities decreased and effective diffusivities were not accelerated by the dextran grafting.Thus, this work clarified that grafted dextran could not accelerate h Ig G uptake rate on the affinity resins, or in other words, chain delivery did not occur on the specific interaction-based affinity adsorption.展开更多
文摘目的:观察葡聚糖接枝聚乳酸载吗啡缓释纳米粒胶束(MP/DEX-PLA)对急性疼痛大鼠的镇痛效应。方法:SD雄性大鼠40只,随机均分为4组,A组(空白对照组),B组(空白纳米胶束对照组),C组(普通吗啡组),D组(载吗啡纳米胶束组)。制备可生物降解的载吗啡葡聚糖接枝聚乳酸共聚物,皮下用药后测定急性疼痛大鼠的累计疼痛评分(CPS)和痛阈,评价药物的镇痛效果,观察其副作用。结果:MP/DEX-PLA纳米胶束呈球形,平均载药量为20.94%,平均包封率为36.27%。建模手术后,各组大鼠痛阈明显降低(P<0.05);给药后,C组和D组CPS明显低于B组,痛阈明显升高(P<0.05);C组和D组分别于给药后30 m in和2h时达到最大镇痛效应,C组镇痛持续时间明显短于D组(P<0.05),C组和D组痛阈最高值和CPS无明显差异(P>0.05),C组不良反应发生率显著高于D组(P<0.05)。结论:皮下单次给予MP/DEX-PLA可通过吗啡缓慢释放发挥持续镇痛作用,副作用小于普通吗啡。
基金Supported by the National Natural Science Foundation of China(21236005,21621004)
文摘Our previous studies have reported the presence of "chain delivery" effects of protein adsorption onto ion exchangers with polymer-grafted ion-exchange groups, such as dextran-grafted and poly(ethylenimine)-modified Sepharose gels. However, it is unclear if the "chain delivery" occurs on affinity adsorption with specific interactions. This work is designed to address this issue. A dextran-grafted Sepharose gel was prepared, and then the matrix was modified using diethylaminoethyl, a typical ion-exchange group, or octapeptide(FYCHWQDE), an affinity ligand for human immunoglobulin G(h Ig G) to prepare ion-exchange or affinity adsorbents, respectively.Results of h Ig G adsorption showed that the uptake rate represented by the effective diffusivity of h Ig G onto the dextran-grafted ion exchangers was obviously enhanced by the dextran grafting, indicating the presence of"chain delivery" of the bound proteins on the charged groups on the dextran chains. By contrast, the effective diffusivity of h Ig G changed little as ligand density increased on the dextran-grafted FYCHWQDE adsorbents.Their adsorption capacities decreased and effective diffusivities were not accelerated by the dextran grafting.Thus, this work clarified that grafted dextran could not accelerate h Ig G uptake rate on the affinity resins, or in other words, chain delivery did not occur on the specific interaction-based affinity adsorption.
