Kim Jong Min, Seo Kwang Su, Jeong Yong Kyun, Hai Bang Lee, Kim Yong Sik, Khang Gilson
Department of Advanced Organic Materials Engineering, Chonbuk National University, 664-14 Dukjin, Jeonju 561-756, South Korea.
J Biomater Sci Polym Ed. 2005;16(8):991-1007. doi: 10.1163/1568562054414676.
The objective of this study was to investigate the effect of aqueous solubility of model drugs and glycolide monomer (GM) from poly(D,L-lactide-co-glycolide) (PLGA) discs on in vitro release rates and polymer degradation. 5-Fluorouracil (5-FU), a water-soluble compound, and dexamethasone in a water-insoluble base form were selected as model drugs. Glycolide monomer, that has moderate solubility in water, was a non-toxic and biodegradable additive as a derivative material of hydrolysis of PLGA in order to obtain desirable drugs release rates. PLGA discs with or without GM were formulated by means of compression molding method. The prepared polymeric discs were incubated at 37 degrees C in phosphate-buffered saline (PBS, pH 7.4) and characterized at scheduled time points for water uptake, mass loss, diameter and morphology change, molecular weight and composition change using scanning electron microscopy (SEM), gel-permeation chromatography (GPC), and H-NMR, respectively. The supernatants were taken out of the sample vials and were analyzed for drug release. The 5-FU release was found to be increasing in proportion to the drug loading amount with an initial burst for 5 days, while dexamethasone release showed inverse relationship with the increasing drug loading amount. However, the release behaviors of 5-FU and dexamethasone polymeric discs containing GM showed faster release rates than control discs (without GM) and did not show lag periods during the in vitro release test due to adding GM, which acted as a channeling agent that has moderate solubility in water. Polymer degradation was found to be affected by aqueous solubility of drugs and GM. In conclusion, we observed that drugs release rates were influenced by their aqueous solubility and loading amount and also GM plays a major role in controlling drug release rates regardless of solubility of drugs. This system appears to be promising for controlled drug delivery aimed at local therapy.
本研究的目的是调查模型药物的水溶性以及聚（D，L-丙交酯-共-乙交酯）（PLGA）圆盘状制剂中的乙交酯单体（GM）对体外释放速率和聚合物降解的影响。选择水溶性化合物5-氟尿嘧啶（5-FU）和水不溶性碱形式的地塞米松作为模型药物。乙交酯单体在水中具有适度的溶解度，作为PLGA水解的衍生材料，是一种无毒且可生物降解的添加剂，以获得理想的药物释放速率。通过压缩成型法制备含或不含GM的PLGA圆盘状制剂。将制备好的聚合物圆盘状制剂在37℃的磷酸盐缓冲盐水（PBS，pH 7.4）中孵育，并在预定时间点分别使用扫描电子显微镜（SEM）、凝胶渗透色谱（GPC）和H-NMR对其进行表征，以测定吸水率、质量损失、直径和形态变化、分子量和组成变化。从样品瓶中取出上清液并分析药物释放情况。发现5-FU的释放量与药物负载量成正比，最初5天有一个突释，而地塞米松的释放与药物负载量的增加呈反比关系。然而，含GM的5-FU和地塞米松聚合物圆盘状制剂的释放行为比对照圆盘状制剂（不含GM）更快，并且在体外释放试验中由于添加了GM而没有显示出滞后阶段，GM作为一种在水中具有适度溶解度的通道剂。发现聚合物降解受药物和GM的水溶性影响。总之，我们观察到药物释放速率受其水溶性和负载量的影响，并且GM在控制药物释放速率方面也起着主要作用，而与药物的溶解度无关。该系统对于旨在局部治疗的控释给药似乎很有前景。
