Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences , Shiraz , Iran.
Drug Dev Ind Pharm. 2013 Nov;39(11):1774-82. doi: 10.3109/03639045.2012.736518. Epub 2012 Nov 9.
Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63 ± 0.57 and 75.19 ± 2.65, respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin addition time of 3 min leaded to 74.1 ± 0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63 ± 1.87, maximum LE of 73.81 ± 3.13 and the slowest drug release with 63.71 ± 3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63 ± 0 and 74.21 ± 1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500 rpm resulted in constant enhancement of LE from 58.3 ± 3.6 to 74.4 ± 2.59 as well as remarkable decrease in size from 148 ± 4.88 to 63 ± 2.64.
今天，在所有纳米药物传递研究中，开发优化的纳米粒子（NP）制备程序至关重要，这将导致更多操作性和临床验证的纳米药物的扩展。在这项研究中，使用单因素实验方法评估了各种制备因素对肝素和壳聚糖之间离子凝胶化制备的水凝胶 NP 的粒径、载药量和药物释放的影响。当改变壳聚糖分子量、壳聚糖浓度、肝素加入壳聚糖溶液的时间、肝素浓度、壳聚糖溶液 pH 值、温度和混合速度等因素，而其他因素处于最佳条件时，评估了 NP 的粒径、载药量和药物释放曲线。结果表明，粒径和载药量高度受壳聚糖浓度的影响，当壳聚糖浓度为 0.75mg/ml 时，分别获得最佳的 63±0.57 和 75.19±2.65。此外，肝素加入壳聚糖溶液的时间为 3min 时，载药量为 74.1±0.79%，对粒径和释放曲线没有明显影响。此外，pH 值为 5.5 时，粒径最小为 63±1.87，载药量最大为 73.81±3.13，在一周内药物释放最慢，为 63.71±3.84%。虽然载药量不受温度影响，但当温度从 25°C 升高到 55°C 时，粒径和释放分别降至 63±0 和 74.21±1.99%。此外，当混合器转速从 500rpm 连续增加到 3500rpm 时，载药量从 58.3±3.6 持续增加到 74.4±2.59，粒径从 148±4.88 显著减小到 63±2.64。
