高压静电场技术制作藻酸钙载药微球及其性能研究
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摘要
目的探索高压静电场技术制备藻酸钙微球的最佳参数组合,以期微球直径更小更均匀,并研究其载药后的缓释行为。方法设置不同的电压、CaCl_2浓度、藻酸钠浓度、离心机转速、针头直径,观察微球直径和表面形态,以直径更小更均匀为标准,筛选最佳参数组合。负载低(L组)、中(M组)、高(H组)3种浓度的牛血清白蛋白,对比3组的包封率和载药率,并绘制累计缓释曲线,观察其体外缓释行为。结果 16 KV电压、1M CaCl_2浓度、0.5%藻酸钠浓度、200 r/min和30 G的针头是最佳参数组合。L、M、H各组的包封率分别为(91±1.46)%、(85±1.63)%和(79±3.29)%,载药率分别为(0.89±0.04)%、(2.56±0.57)%和(4.10±1.21)%。3组药物都可以持续释放超过28 d,缓释时间较长,释放行为稳定、规律。结论利用最佳参数组合制备的藻酸钙微球是一种优良的药物缓释载体。
Objective To explore the optimal combination parameters of calcium alginate microspheres by using high voltage electrostatic field technology, and to make microspheres with smaller and more uniform diameters for further study of the sustained release behavior of microspheres after drug loading. Methods Different voltage, CaCl_2 concentration, and sodium alginate concentration were set. The centrifuge speed and needle diameter were observed. The diameter and surface morphology of the microspheres were observed. The optimal combination parameters were selected with smaller and more uniform diameters. Low, medium and high loads, three concentrations of bovine serum albumin, were named group L, group M and group H respectively. The encapsulation efficiency and drug loading rate of the three groups were compared. The cumulative slow-release curve was drawn and the sustained-release behavior in vitro was observed. Results Voltage of 16 KV, 1 M CaCl_2 concentration, 0.5% sodium alginate concentration, 200 r/min and 30 G needle were the best combination parameters. The encapsulation rates of group L, M and H were(91 ±1.46)%,(85±1.63)%,(79±3.29)% respectively. And the drug loading rates were(0.89±0.04)%,(2.56±0.57)%,(4.10±1.21)% respectively. All the three groups of drugs could be sustained for more than 28 days, the sustained release time was longer, and the release behavior was stable and regular.Conclusion The calcium alginate microspheres produced by using the optimal combination parameters are excellent drug delivery vehicles.
Objective To explore the optimal combination parameters of calcium alginate microspheres by using high voltage electrostatic field technology, and to make microspheres with smaller and more uniform diameters for further study of the sustained release behavior of microspheres after drug loading. Methods Different voltage, CaCl_2 concentration, and sodium alginate concentration were set. The centrifuge speed and needle diameter were observed. The diameter and surface morphology of the microspheres were observed. The optimal combination parameters were selected with smaller and more uniform diameters. Low, medium and high loads, three concentrations of bovine serum albumin, were named group L, group M and group H respectively. The encapsulation efficiency and drug loading rate of the three groups were compared. The cumulative slow-release curve was drawn and the sustained-release behavior in vitro was observed. Results Voltage of 16 KV, 1 M CaCl_2 concentration, 0.5% sodium alginate concentration, 200 r/min and 30 G needle were the best combination parameters. The encapsulation rates of group L, M and H were(91 ±1.46)%,(85±1.63)%,(79±3.29)% respectively. And the drug loading rates were(0.89±0.04)%,(2.56±0.57)%,(4.10±1.21)% respectively. All the three groups of drugs could be sustained for more than 28 days, the sustained release time was longer, and the release behavior was stable and regular.Conclusion The calcium alginate microspheres produced by using the optimal combination parameters are excellent drug delivery vehicles.
引文
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[2]单连海,郭海霞,张志斌.海藻酸钠微球的制备及对BSA控制释放的实验[J].重庆理工大学学报(自然科学版),2010,24(9):34-37.
[3]吴秋惠,吴皓,王令充,等.海藻酸钠微球的制备及其在药物载体中的应用进展[J].中华中医药杂志,2011,26(8):1791-1794.
[4]韩舒,杨军星,宋志光,等.藻酸盐缓释微球的研究进展[J].口腔医学研究,2014,30(11):1107-1109.
[5]Shi PJ,He PF,Thomas KH,et al.Parametric analysis of shape changes of alginate beads[J].Powder Technol,2011,210(1):60-66.
[6]Zhang H,Pu C,Wang Q,et al.Physicochemical characterization and pharmacokinetics of agomelatine-loaded PLGA microspheres for intramuscular injection[J].Pharm Res,2018,36(1):9.
[7]Xing L,Sun J,Tan H,et al.Covalently polysaccharide-based alginate/chitosan hydrogel embedded alginate microspheres for BSA encapsulation and soft tissue engineering[J].Int J Biol Macromol,2019,127:340-348.
[8]Jain D,Bar-Shalom D.Alginate drug delivery systems:application in context of pharmaceutical and biomedical research[J].Drug Dev Ind Pharm,2014,40(12):1576-1584.
[9]Nikoo AM,Kadkhodaee R,Ghorani B,et al.Electrospray-assisted encapsulation of caffeine in alginate microhydrogels[J].Int J Biol Macromol,2018,116:208-216.
[10]Cho A,Chun Y,Kim B,et al.Preparation of alginate-CaCl2microspheres as resveratrol carriers[J].J Mater Sci,2014,49(13):4612-4619.
[11]Maestrelli F,Mura P,González-Rodríguez ML,et al.Calcium alginate microspheres containing metformin hydrochloride niosomes and chitosomes aimed for oral therapy of type 2diabetes mellitus[J].Int J Pharm,2017,530(1-2):430-439.
[12]Prabhakaran MP,Zamani M,Felice B,et al.Electrospraying technique for the fabrication of metronidazole contained PLGAparticles and their release profile[J].Mater Sci Eng C Mater Biol Appl,2015,56:66-73.
[13]Gasmi H,Siepmann F,Hamoudi MC,et al.Towards a better understanding of the different release phases from PLGAmicroparticles:Dexamethasone-loaded systems[J].Int J Pharm,2016,514(1):189-199.